DigitalUM :: Browsing by Subject "Proliferation"

Browsing by Subject "Proliferation"

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Open Access
A Side-by-Side comparison of wildtype and variant melanocortin 1 receptor signaling with emphasis on protection against oxidative damage to DNA.
(MDPI, 2023-09-21) Cerdido, Sonia; Sánchez-Beltrán, José; Lambertos, Ana; Abrisqueta, Marta; Padilla, Lidia; Herraiz Serrano, Cecilia María; Jiménez-Cervantes, Celia; García-Borrón, José Carlos; Olivares, Conchi; Bioquímica y Biología Molecular B e Inmunología
Common variants of the MC1R gene coding the α-melanocyte stimulating hormone receptor are associated with light skin, poor tanning, blond or red hair, and increased melanoma risk, due to pigment-dependent and -independent effects. This complex phenotype is usually attributed to impaired activation of cAMP signaling. However, several MC1R variants show significant residual coupling to cAMP and efficiently activate mitogenic extracellular signal-regulated kinase 1 and 2 (ERK1/2) signaling. Yet, residual signaling and the key actions of wildtype and variant MC1R have never been assessed under strictly comparable conditions in melanocytic cells of identical genetic background. We devised a strategy based on CRISPR-Cas9 knockout of endogenous MC1R in a human melanoma cell line wildtype for BRAF, NRAS and NF1, followed by reconstitution with epitope-labeled MC1R constructs, and functional analysis of clones expressing comparable levels of wildtype, R151C or D294H MC1R. The proliferation rate, shape, adhesion, motility and sensitivity to oxidative DNA damage were compared. The R151C and D294H RHC variants displayed impaired cAMP signaling, intracellular stability similar to the wildtype, triggered ERK1/2 activation as effectively as the wildtype, and afforded partial protection against oxidative DNA damage, although less efficiently than the wildtype. Therefore, common melanoma-associated MC1R variants display biased signaling and significant genoprotective activity.
Open Access
ABRACL upregulated by transcription factor CBX4 promotes proliferation and migration and inhibits the apoptosis of gastric cancer cells
(Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2025) Guo, Kai; Gao, Xiao
Background. Gastric cancer (GC) is a predominant health concern in many countries. Actin-binding Rho activating C-terminal-like (ABRACL) belongs to a new family of low molecular weight proteins and has been implicated in cancers. This study was implemented to elucidate the role and mechanism of ABRACL in GC. Methods. The mRNA and protein expression of ABRACL and CBX4 in human gastric epithelium cell line GES-1 and GC cell lines was assessed with RT-qPCR and western blot. The transfection efficacy of sh-ABRACL, oe-CBX4, and sh-CBX4 was examined with RT-qPCR and western blot. AGS cell proliferation, migration, and invasion were evaluated using CCK-8, colony formation assay, wound healing, and Transwell assays, respectively. With western blot analysis, flow cytometry, and caspase-3 assay kits, the expressions of MMP2 and MMP9, cell apoptosis, and caspase-3 activity were estimated. Western blot was adopted to estimate the contents of apoptosis-related proteins. Luciferase reporter and chromatin immunoprecipitation (ChIP) were applied to verify the interaction between ABRACL and CBX4. Results. The expression of ABRACL and CBX4 was increased in GC tissues and cells. After interfering with ABRACL, the proliferation, migration, and invasion of GC cells were inhibited while apoptosis was promoted. We also discovered that CBX4 could bind to ABRACL and transcriptionally regulate ABRACL expression in AGS cells. Rescue experiments revealed that CBX4 overexpression partially reversed the regulatory effects of ABRACL silencing on the proliferation, migration, invasion, and apoptosis of GC cells. Conclusion. Collectively, ABRACL transcriptionally upregulated by CBX4 promoted the malignant progression of GC.
Open Access
Abundant proliferating cells within early chicken taste buds indicate a potentially "built-in" progenitor system for taste bud growth during maturation in hatchlings
(Universidad de Murcia. Departamento de Biología Celular e Histología, 2019) Wang, Zhonghou; Yoshida, Yuta; Kramer, Naomi E.; Kawabata, Fuminori; Tabata, Shoji; Kim, Woo K.; Liu, Hong-Xiang
Like other epithelial cells, taste bud cells have a short life span and undergo continuous turnover. An active stem or progenitor cell niche is essential for taste bud formation and maintenance. Early taste bud cells have a life span of ~4 days on average in chicken hatchlings when taste buds grow rapidly and undergo maturation. The average life span is shorter than that of mature taste bud cells of rodents (~10-12 days on average). To better understand the mechanism underlying taste bud growth and homeostasis in chickens, we analyzed the distribution of proliferating cells in different tissue compartments, including taste buds, the surrounding epithelium and the underlying connective tissue in post-hatch (P)1-3 hatchlings and P45 chickens. Unlike rodents, which lack proliferating cells within both early and mature taste buds, chickens possessed abundant proliferating cells within early taste buds. Further, at P45, when taste buds are mature and undergo continuous cell renewal, taste buds also contained proliferating cells, though to a lesser extent. These proliferating cells in early taste buds, indicated by PCNA+ and BrdU+ cells, primarily localized to the basal region of taste buds and were largely unlabeled by the two known molecular markers for chicken taste bud cells (Vimentin and α-Gustducin), suggesting their undifferentiated status. Our data indicate that early chicken taste buds have “built-in” progenitors in order to grow to and maintain their large size and rapid cell turnover in hatchlings.
Open Access
Akt1 and Akt2: Differentiating the aktion
(Murcia: F. Hernández, 2011) Heron-Milhavet, Lisa; Khouya, Nabil; Fernandez, Anne; Lamb, Ned J.
Kinases of the Akt family are integral and essential components in growth factor signaling pathways activated downstream of the membrane bound phospho-inositol-3 kinase. In light of strong homologies in the primary amino acid sequence, the three Akt kinases were long surmised to play redundant and overlapping roles in insulin signaling across the spectra of cell and tissue types. Over the last 10 years, work using mouse knockout models, cell specific inactivation, and more recently targeted gene inactivation, has brought into question the redundancy within Akt kinase isoforms and instead pointed to isoform specific functions in different cellular events and diseases. Here we concentrate on the differential roles played by Akt1 and Akt2 in a variety of cellular processes and in particular during cancer biogenesis. In this overview, we illustrate that while Akt1 and 2 are often implicated in many aspects of cellular transformation, the two isoforms frequently act in a complementary opposing manner. Furthermore, Akt1 and Akt2 kinases interact differentially with modulating proteins and are necessary in relaying roles during the evolution of cancers from deregulated growth into malignant metastatic killers. These different actions of the two isoforms point to the importance of treatments targeting isoform specific events in the development of effective approaches involving Akt kinases in human disease.
Open Access
Apoptosis and proliferation of the prostate cells in men with benign prostatic hyperplasia and concomitant metabolic disorders
(Universidad de Murcia. Departamento de Biología Celular e Histología, 2018) Rył, Aleksandra; Rotter, Iwona; Kram, Andrzej; Teresiński, Leszek; Słojewski, Marcin; Dołęgowska, Barbara; Lubkowska, Anna; Piasecka, Małgorzata; Laszczyńska, Maria
Introduction. Apoptosis and proliferation of prostate cells are associated with both physiological increase and hyperplasia of the prostate. The aim of this study was to determine the contribution of metabolic syndrome to the processes of apoptosis and proliferation in gland epithelial cells and prostatic stromal cells in men with BPH. Materials and methods. The study involved 151 men, aged 52-89 years, receiving pharmacological treatment for BPH. The men were divided into two groups: those with and those without metabolic syndrome. The serum levels of the parameters were determined. Reactions for the identification of apoptosis (TUNEL) and proliferation (PCNA) in cells were also performed. Results. The relationships between the number of TUNEL(+) and PCNA(+) cells and metabolic syndrome were not observed. It was found that the total number of TUNEL(+) cells in the prostate stroma correlated negatively with the levels of highdensity lipoprotein and insulin-like growth factor-1. The analysis of the correlations in BPH patients with and without metabolic syndrome demonstrated that the only parameter correlating with the number of PCNA(+) cells in the prostate stroma was insulin resistance. Conclusion. Metabolic syndrome in patients with BPH had no impact on the number of TUNEL(+) and PCNA(+) cells in the prostate gland. However, the disturbed levels of metabolic parameters, and deviations of anthropometric parameters from normal may influence the number of apoptotic and proliferating cells.
Open Access
Chk1/2 inhibitor AZD7762 blocks the growth of preantral follicles by inducing apoptosis, suppressing proliferation, and interfering with the cell cycle in granulosa cells
(Universidad de Murcia. Departamento de Biología Celular e Histología, 2023) Liu, Xiao Ming; Chen, Fang; Zhang, Fan; Zhao, Jun Zhao
Background. Checkpoint kinases 1/2 (Chk1/2) have an important role in somatic cell development and oocyte meiotic maturation. However, the role of Chk1/2 in folliculogenesis has not been fully elucidated. The aim of this study was to assess the effects of Chk1/2 inhibition on ovarian folliculogenesis and granulosa cell development in mice. Methods. Preantral follicles (100-120 μm) and granulosa cells from pre-ovulatory follicles (pre-GCs) of mice were isolated and cultured with or without Chk1/2 inhibitor AZD7762. Preantral follicles were cultured for 96h. Then, follicle morphology and follicular growth were assessed every 48h. Granulosa cells were cultured for 48h with or without AZD7762, after which cell apoptosis, cell proliferation, and cell cycle analysis were assessed; meanwhile, the mRNA expression of PCNA and Bax were measured by real-time RT-PCR, and PCNA and Bax protein were measured by Western blot. Results. Compared with control follicles, AZD7762 inhibited growth of preantral follicles (P<0.05). Furthermore, inhibition of Chk1/2 significantly induced apoptosis (P<0.05) and inhibited the proliferation of granulosa cells (P<0.01), arrested cell cycle at S and G2/M phases, and decreased G1 phase fraction (P<0.001). Also, the expression of PCNA mRNA and protein were reduced (P<0.01), while Bax mRNA and protein were increased (P<0.05) post AZD7762 treatment in granulosa cells. Conclusions. This study revealed that Chk1 and Chk2 have a crucial role during preantral follicular development by regulating the proliferation and apoptosis of granulosa cells.
Open Access
CircRNA PDE3B regulates tumorigenicity via the miR-136-5p/MAP3K2 axis of esophageal squamous cell carcinoma
(Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2023) Yue, Wei; Ye, Yiwang; Chen, Baokun; Wu, Da; Wang, He; Hui, Gang
Background. CircRNA has a covalently closed circular conformation and a stable structure. However, the exact role of circRNA in esophageal squamous cell carcinoma (ESCC) remains uncertain. The purpose of this study was to explore the role of hsa_circ_0000277 (circ_PDE3B) in ESCC. Methods. The expression levels of circ_PDE3B, miR-136-5p and mitogen-activated protein kinase kinase kinase 2 (MAP3K2) in ESCC tissues and cells were detected by quantitative real-time polymerase chain reaction (qRT-PCR) or western blot. The proliferation ability of EC9706 and KYSE30 cells was detected by clonal formation, 5-ethynyl-2’-deoxyuridine (EdU) and 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-Htetrazolium bromide (MTT) assays. Flow cytometry was used to detect the apoptosis rate of cells. Transwell assay was used to detect the invasion ability of EC9706 and KYSE3 cells. The relationship between miR-136-5p and circ_PDE3B or MAP3K2 was verified by dual-luciferase reporter assay and RNA pull-down, and the effect of circ_PDE3B on tumor growth in vivo was explored through tumor transplantation experiment. Immunohistochemistry (IHC) assay was used to detect MAP3K2 and Ki67 expression in mice tumor tissues. Results. The results showed that circ_PDE3B was highly expressed in ESCC tissues and cells. Downregulated circ_PDE3B expression in ESCC cells significantly reduced cell proliferation, migration and invasion. Circ_PDE3B served as a sponge for miR-136- 5p, and miR-136-5p inhibition reversed the roles of circ_PDE3B knockdown in ESCC cells. MAP3K2 was a direct target of miR-136-5p, and miR-136-5p targeted MAP3K2 to inhibit the malignant behaviors of ESCC cells. Furthermore, circ_PDE3B regulated MAP3K2 expression by sponging miR-136-5p. Importantly, circ_PDE3B knockdown inhibited tumor growth in vivo. Conclusions. In conclusion, circ_PDE3B acted as oncogenic circRNA in ESCC and accelerated ESCC progression by adsorption of miR-136-5p and activation of MAP3K2, supporting circ_PDE3B as a potential therapeutic target for ESCC.
Open Access
Combining enamel matrix proteins with mechanical stimuli potentiates human periodontal ligament fibroblasts proliferation and periodontium remodeling
(Universidad de Murcia. Departamento de Biología Celular e Histología, 2018) Zou, Rui; Wan, Wanting; Li, Jingjing; Du, Chanyuan; Wang, Yijie; Qian, Tian; Niu, Lin
Background. Collagen I (Col-I) and matrix metalloproteinase-1 (MMP-1) have been implicated in the regeneration and remodeling of the periodontium. Studies have shown that enamel matrix proteins (EMPs) and mechanical stimuli can promote the synthesis and degradation, respectively, of Col-I and MMP-1. However, the effects of the combination of EMPs and mechanical stimuli on human periodontal ligament are not known. Objective. Our aim was to test the combined effects of EMPs and mechanical stimuli on the proliferation of human periodontal ligament fibroblasts (HPDLFs) and Col-I and MMP-1 mRNA expression. Methods. Primary HPDLFs were isolated using an enzyme digestion method. To select the optimum EMP concentration and the optimum magnitude and loading time of mechanical stimuli, HPDLFs were stimulated with gradient concentration of EMPs (0 µg/mL, 25 µg/mL, 50 µg/mL, 100 µg/mL and 200 µg/mL) and mechanical stimuli (0 kPa, 25 kPa, 50 kPa, 100 kPa, and 200 kPa for 0 h, 3 h, 6 h, 12 h, and 24 h), respectively. The cell proliferative response was tested by the MTT assay. The impact of EMPs combined with mechanical stimuli on Col-I and MMP-1 mRNA expression were measured by reverse transcription polymerase chain reaction. Results. 100 µg/mL of EMPs and a 50 kPa mechanical stimulus were chosen as the optimum parameters due to the higher proliferation rates than other doses. The combination of 100 µg/mL of EMPs and a 50 kPa mechanical stimulus significantly stimulated HPDLFs proliferation and increased Col-I and MMP-1 expression levels compared with incubation with two factors alone. Conclusions. We concluded that the combination of EMPs and mechanical stimulus have synergistic effects on cell growth, cell number, collagen turnover, and periodontium remodeling.
Open Access
D-2-hydroxyglutarate dehydrogenase in breast carcinoma as a potent prognostic marker associated with proliferation
(Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2021) Hayashi, Chiaki; Takagi, Kiyoshi; Sato, Ai; Yamaguchi, Mio; Minemura, Hiroyuki; Miki, Yasuhiro; Harada-Shoji, Narumi; Miyashita, Minoru; Sasano, Hironobu; Suzuki, Takashi
Background. D-2-hydroxyglutarate dehydrogenase (D2HGDH) catalyzes D-2-hydroxyglutarate to α-ketoglutarate and is involved in the regulation of cellular energy and biosynthetic intermediates. Previously, D2HGDH was reported to decrease 2-hydroxyglutarate level in breast carcinoma cells, but no other report has examined D2HGDH in breast carcinoma, and its significance remains unknown. Methods. We first immunolocalized D2HGDH in 224 invasive breast carcinomas and evaluated its clinicopathological significance. We next examined associations between gene expression of D2HGDH and α-ketoglutarate-dependent dioxygenases in 23 breast carcinoma tissues using the gene expression profile data. Finally, we examined the effects of D2HGDH on the proliferation in three breast carcinoma cells. Results. D2HGDH immunoreactivity was detected in 49% of invasive breast carcinomas, and the immunohistochemical D2HGDH status was positively associated with histological grade, HER2 and Ki-67, while it was inversely associated with estrogen receptor. Moreover, it was significantly associated with worse prognosis of the breast cancer patients, and it turned out to be an independent prognostic factor for both the disease-free and breast cancer-specific survival in these patients. Gene expression profile data revealed that D2HGDH expression was positively associated with the expression of 6 α-ketoglutarate-dependent dioxygenases (KDM3A, PLOD1, EGLN2, ALKBH1, ASPH and ALKBH7). Consequent in vitro experiments demonstrated that D2HGDH overexpression significantly increased the cell proliferation activity of MCF-7, T47D and MDA-MB-231 cells. Conclusion. These results suggest that D2HGDH plays an important role in the growth of breast carcinoma, possibly through regulating functions of αketoglutarate-dependent dioxygenases, and that D2HGDH status is a potent worse prognostic factor in breast cancer patients
Open Access
Downregulation of miR-485-3p promotes proliferation, migration and invasion in prostate cancer through activation of TGF-β signaling
(Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2022) Chen, Dongdong Chen; Fan, Jiaxing; Li, Xianduo; Jiao, Zongshuai; Tang, Guanbao; Guo, Xuewen; Chen, Hao; Wang, Jianning; Men, Tongyi
Background. Prostate cancer (PC) is the second leading cause of cancer-related death among men worldwide. Downregulation of miR-485-3p has been revealed to participate in the tumorigenesis and progression of many types of cancer. However, the clinical and biological role of miR-485-3p in PC remains largely unknown. Methods. The expression of miR-485-3p was analyzed in the published databases and detected in our clinical samples and cell lines by RT-qPCR assay. CCK8, transwell invasion and migration, and colony formation assays were performed to investigate the biological function of miR-485-3p. Bioinformatical analysis, RIP, western blotting and luciferase reporter assays were carried out to explore the downstream mechanism of miR-485-3p. Results. The level of miR-485-3p was downregulated in PC tissues, particularly in primary PC tissues with metastasis relative to normal prostate tissues. miR-485-3p downregulation was positively correlated with poor disease-free and overall survival in patients with PC. Functionally, miR-485-3p overexpression dramatically suppressed the proliferation, migration and invasion ability of PC cells in vitro. Mechanistically, miR-485-3p overexpression suppressed the activity of TGF-β signaling by targeting TGFBR2 to play tumor-suppressive roles in PC progression. Conclusion. Our study reports the miR-485- 3p/TGFBR2/ TGF-β signaling axis in tumor development of PC, suggesting miR-485-3p may be a potential target to develop therapeutic strategies against PC.
Open Access
Enhanced IL-10 inhibits proliferation and promotes apoptosis of HUVECs through STAT3 signaling pathway in sepsis
(Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2021) Xie, Zuohua; Lin, Bing; Jia, Xinju; Su, Ting; Wei, Ying; Tang, Jiping; Yang, Chengzhi; Cui, Chuanbao; Liu, Jinxiang
Aims. The present study aims to determine the expression of interleukin (IL)-10 in peripheral blood of patients with sepsis, and investigate its effects on the biological function of vascular endothelial cells. Methods. Thirty-six sepsis patients and 20 healthy subjects were included. Peripheral blood was collected from all subjects. ELISA was used to determine IL-10 content in serum. A ratio of IL-10+ T cells was determined by flow cytometry. CCK-8 assay was used to investigate proliferation. Cell cycle and apoptosis were analyzed by flow cytometry. Western blotting was used to examine the expression of phosphorylated STAT3 protein. Results. The content of IL-10 and the ratio of IL-10+ T cells were enhanced in pa-tients with sepsis. Serum from patients with sepsis inhibited the proliferation of HU-VECs, and addition of IL-10 antibody reversed this effect. IL-10 in the serum from patients with sepsis promoted the apoptosis of HUVECs. IL-10 inhibited the proliferation and promoted the apoptosis of HUVECs by enhancing the phosphorylation of STAT3. Conclusions. The present study demonstrates that the content of IL-10 and the ratio of IL-10+ T cells in peripheral blood of patients with sepsis are up-regulated, and this inhibits HUVEC proliferation and promotes HUVEC apoptosis through STAT3 sig-naling pathway. The results in this study provide a new experimental basis for further understanding the molecular mechanism of sepsis-induced vascular injury.
Open Access
Estrogen-mediated dental tissue regeneration
(Universidad de Murcia. Departamento de Biología Celular e Histología, 2016) Lu, Yadie; Jin, Lin; Lei, Gang; Fu, Yujin; Wang, Yanqiu; Yu, Jinhua
As the key regulator of hard tissue metabolism in both men and women, estrogen regulates the processes necessary for cell growth, proliferation, and differentiation through estrogen receptor (ER). Estrogen deficiency usually causes systemic osteoporosis not only in long bones but also in jaw bones, and exogenous estrogen can enhance the osteogenic potential of mesenchymal stem cells. Dental mesenchymal stem cells (DMSCs) represent a group of stem cells isolated from different parts of the tooth, including dental pulps, apical papillae and periodontal ligaments. A number of studies have proved that estrogen plays an important role in the proliferation, differentiation and tissue regeneration of human DMSCs. Thus, this review will focus on the effects of estrogen on proliferation, apoptosis, and differentiation of dental stem cells, discuss evidence from studies in rodents that estrogen plays an important role in dental morphogenesis as well as periodontal remodeling, and suggest directions for future studies in estrogen-related tooth regeneration.
Open Access
Evaluation of morphology, apoptosis, and cell proliferation of the uterus in postmenopausal women
(Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2025) Ratajczak, Weronika; Łazowska, Malwina; Laszczyńska, Maria; Rył, Aleksandra; Lubkowska, Anna; Zimny, Małgorzta; Kram, Andrzej; Sipak, Olimpia
Background. The aim of this study was to evaluate the morphology (atrophy and fibrosis), apopto-sis, and cell proliferation in the uterine wall. The research material came from postmenopausal women who had undergone hysterectomy due to uterine myomas or prolapse of the reproductive organ and were not taking menopausal hormone therapy (MTH). Material and Methods. The collected material was divided into three groups. Group I (n=18) con-sisted of uterine sections taken 1 to 5 years after the last menstruation, Group II (n=17) 6 to 10 years after the last menstruation, and Group III (n=15) over 11 years after the last menstruation. To assess morphology and fibrosis, the uterine sections were subjected to hematoxylin and eosin (HE) staining and to Mallory's staining. In addition, we performed a histochemical examination to identify apopto-sis in endometrial and myometrial cells using the TUNEL method. An immunohistochemical analysis of endometrial and myometrial cells was also performed to detect the location of the proliferating cell nuclear antigen (PCNA). Results. Differences in apoptosis were only found in the myometrium between Group I and Group III, and were strongest in Group I myometrial cells, and weakest in Group III. Neither the endome-trium nor the myometrium showed statistically significant differences in the overall percentage of PCNA(+) cells between groups. Conclusion. Morphological changes in the endometrial and myometrial layers of postmenopausal uteri increased with time since the last menstruation.
Open Access
Expression and clinical significance of RHCG in endometrial cancer
(Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2024) Wang, Huifang; Jin, Haihong; Zhao, Sufen
Endometrial cancer (EC) is the most common gynecological cancer. Rhesus family, C glycoprotein (RHCG) has been evidenced to be involved in the occurrence and development of various tumors. This study aimed to investigate the expression and clinical significance of RHCG in EC. Bioinformatics analysis was based on the RNAseq counts data from TCGA database, and the prognosis analysis was performed using the Kaplan-Meier method; 4 cases of endometrioid adenocarcinomas samples and 4 cases of normal proliferative endometrium were collected for qPCR and western blot; immunohistochemistry analysis was employed to assess the expression of RHCG in a tissue microarray; the correlation between RHCG and clinicopathological factors was analyzed through Mann-Whitney U test. The lentiviral interference vector was further constructed. The results demonstrated that RHCG was highly expressed in EC tissues, and RHCG was an independent factor affecting the overall survival of patients. Additionally, the expression of RHCG was related to FIGO stage and tumor infiltrate. After interfering with shRHCG, the proliferation activity of EC cells decreased, the migration ability of cells decreased, the apoptosis of cells increased, and the tumor outgrowth was arrested. In summary, RHCG promotes the malignant proliferation and migration of EC, and makes the cells have anti-apoptotic activity. Our study provides a theoretical basis for RHCG to become a potential therapeutic target for EC in the future
Open Access
Expression of glucose-regulated protein 78 as prognostic biomarker for triple-negative breast cancer
(Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2020) Yang, Chenlian; Zhang, Zhiwei; Zou, Yutian; Gao, Guanfeng; Liu, Lingrui; Xu, Haifan; Liu, Feng
Introduction. glucose-regulated protein78 (GRP78) is a stress - induced endoplasmic reticulum chaperone protein. It is closely related to the occurrence, development, proliferation, differentiation and drug resistance of breast cancer. However, the association and clinicopathological features between GRP78 and triple negative breast cancer (TNBC) remain to be studied. Material and Methods. Clinical and pathological characteristics and overall survival were analysed retrospectively in 179 surgically resected TNBC patients. GRP78 was detected by immunohistochemistry (IHC) using breast cancer tissue microarrays (TMAs), and the association between GRP78 levels and clinicopathological factors and prognosis was analyzed. Furthermore, GRP78 expression in human TNBC and NTNBC cell lines was detected by Western blot and qRT-PCR. After Si-GRP78 knocked-down GRP78 in MDA-MB-231 and BT549 cell lines, cell proliferation was detected using Cell Counting Kit-8 (CCK-8) and cell colony formation was detected by crystal violet staining, respectively. Results. GRP78 was expressed in triple negative breast cancer (TNBC). GRP78 expression was significantly associated with invasive, distant metastasis and proliferation of TNBC (P<0.05). In addition, patients with positive GRP78 expression had shorter overall survival (OS) and disease-free survival (DFS). And the high expression of GRP78 was significantly associated with disease-free survival (DFS) in patients with TNBC (P<0.001). Conclusions. These findings improve our understanding of the expression pattern of GRP78 in TNBC and clarify the role of GRP78 as a promising prognostic biomarker for triple-negative breast cancer.
Open Access
Fibroblast activation protein-alpha knockdown suppresses prostate cancer cell invasion and proliferation
(Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2022) An, Jiali; Hou, Dingkun; Wang, Lei; Wang, Lili; Yang, Yuanyuan; Wang, Haitao
Background. Prostate cancer is one of the most common malignant tumors of the male genitourinary system. Fibroblast activation protein alpha (FAP-α) overexpression has been shown to occur in a wide range of tumors. However, the specific mechanism of FAP-α in the development of prostate cancer has not been reported. Methods. In this study, real-time quantitative PCR (qRT-PCR) was used to detect the relative expression of FAP-α mRNA in prostate cancer cell lines (PC-3, LNCaP, and DU145) and human normal prostate epithelial cell line RWPE-1. Small interfering RNA (siRNA) targeting FAP-α and vectors expressing exogenous FAP-α were transfected to prostate cancer cells (LNCaP and DU145) to investigate the function of FAP-α. BALB/c nude mice were injected with DU145 cells which were transfected with NC-siRNA, FAP-αsiRNA-1, or FAP-α-siRNA-2. Results. Compared to adjacent normal tissues, FAPα protein and mRNA levels in prostate cancer tissues increased significantly (P<0.05). Compared to patients with high FAP-α mRNA levels, patients with low FAP-α mRNA levels had a significantly higher survival rate (χ2=5.050, log-rank P=0.025). Overexpression of FAP-α in LNCaP cells markedly inhibited cell apoptosis, and promoted cell invasion and proliferation. In contrast, knockdown of FAP-α expression in DU145 cells can significantly reduce invasion, proliferation, and promote apoptosis in prostate cancer. Immunofluorescence assay further indicated that down-regulation of FAP-α could suppress the nuclear translocation of β-catenin. An in vivo study found that compared with the NC-siRNA group, the tumor weight and tumor volume in the FAPα-siRNA-1 and FAP-α-siRNA-2 groups were significantly decreased. Conclusions. In conclusion, down-regulation of FAP-α can inhibit the invasion and proliferation of prostate cancer. Our study provides a theoretical basis for the targeted treatment of prostate cancer.
Open Access
Gamma-aminobutyric acid GABA and cell proliferation, focus on cancer cells
(Murcia : F. Hernández, 2006) Watanabe, M.; Maemura, K.; Oki, K.; Shiraishi, N.; Shibayama, Y.; Katsu, K.
In addition to its role in the adult mammalian nervous system as an inhibitory neurotransmitter, g-aminobutyric acid (GABA) is involved in the proliferation, differentiation, and migration of several kinds of cells including cancer cells. GABA is synthesized predominantly from glutamate by glutamate decarboxylase and exerts its effects via ionotropic GABAA receptors and/or metabotropic GABAB receptors. In this review, the current state of knowledge regarding the role of the GABAergic system in peripheral nonneuronal cell proliferation is described, and recent advances in elucidation of the mechanisms leading to cell proliferation are discussed.
Open Access
GPBAR1 promotes proliferation and is related to poor prognosis of high-grade glioma via inducing MAFB expression
(Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2022) Sun, Suohui; Guo, Hui; Liang, Nan; Wu, Tao; Zhang, Chunpu; Li, Huaqing
Background. Glioma is the most prevalent brain tumors with extremely poor prognosis, but the prognostic biomarkers of high-grade (grade III and IV) gliomas (HGG) are still insufficient. Materials and methods. In our study, we investigated the expression of GPBAR1 in HGG by qRT-PCR and immunohistochemistry (IHC), and evaluated the clinical significance of GPBAR1 with univariate and multivariate analyses. By retrieving the data from TCGA, we screened the genes significantly associated with GPBAR1, and identified the correlation between GPBAR1 and MAFB. By experiments in vitro, we showed the pivotal role of MAFB in GPBAR1-induced proliferation of HGG. Results. GPBAR1 expression in HGGs was significantly higher than that in normal brain tissues. GPBAR1 was an independent prognostic biomarker of HGG. GPBAR1 promoted the proliferation of HGG by inducing MAFB expression. MAFB was also a prognostic biomarker of HGG, and patients with coexpression of MAFB and GPBAR1 had worse prognosis. Conclusions. GPBAR1 promoted the proliferation of HGG by inducing MAFB expression. Both GPBAR1 and MAFB were prognostic biomarkers of HGG, and patients with co-expression of MAFB and GPBAR1 had worse prognosis than those with only GPBAR1 or MAFB expression.
Open Access
Has_circ_0071803 promotes colorectal cancer progression by regulating miR-330-5p/MAPK signaling pathway
(Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2023) Huang, Liyong; Dou, Guangjian; Lu, Jiajun; Chen, Zhiheng; Wang, Jiayi
Colorectal cancer (CRC) is the third most commonly diagnosed cancer worldwide. A lack of effective targeted therapies against CRC makes the treatment challenging. Here, we report a circular RNA (circRNA), has_circ_0071803, functioning as an oncogene in CRC. Circ_0071803 was upregulated in CRC tissues and cell lines, and its expression levels were inversely correlated with the prognosis and survival rate of patients with CRC. Circ_0071803 knockdown suppressed cell proliferation, migration, and invasion in CRC. Moreover, we found that circ_0071803 sponged miR-330-5p, thereby upregulating mitogen-activated protein kinase 1 (MAPK1) in CRC cells. The suppression of cell activities by circ_0071803 knockdown were rescued by miR-330-5p inhibition or MAPK1 overexpression. Collectively, our findings elucidate that circ_0071803 promotes CRC progression by regulating the miR-330-5p/MAPK1 pathway, providing potential therapeutic targets for designing effective targeted treatments
Open Access
High expression of USP18 is associated with the growth of colorectal carcinoma
(Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2021) Zhang, Lin; Zhang, Ningning; Li, Xin; Wu, Wanxin; Zhang, Yanping; Wang, Jingyu
Aim. To investigate whether USP18 can be used as a predictive marker for the diagnosis and development of colorectal cancer. Methods. The Gene Expression Omnibus (GEO) Dataset and the Cancer Genome Atlas (TCGA) database were used to select differential proteins for the ubiquitinspecific peptidases (USPs). The extensive target prediction and network analysis methods were used to assess the association with the USP18 interacting proteins, as well as the statistical correlation between USP18 and the clinical pathology parameters. The effects of USP18 on the proliferation of colorectal cancer were examined using CCK8. The effects of USP18 on the migration of colorectal cancer were examined using wound healing assays. Immunohistochemistry (IHC) was performed on the tissue microarray. Results. The results showed that the expression of USP18 was related to age (P=0.014). The positive rates of the USP18 protein in T1, T2, T3, and T4 were 0.00%, 22.92%, 78.38%, and 95.35%, respectively (P<0.00). The positive rates of the USP18 protein in I, II, III, and IV were 47.43%, 83.12%, 66.67%, and 100.00%, respectively (P<0.00). The Western blot assay showed that the expression of USP18 in colorectal cancer tissues was significantly higher than that in matched paracancerous tissues (P<0.05). The CCK8 experiments suggested that USP18 promoted the migration of CRC cells. Wound healing assays suggested that USP18 promoted the proliferation of CRC cells. Conclusion. This study showed that USP18 can promote the proliferation of colorectal cancer cells and might be a potential biomarker for the diagnosis of CRC.