Histology and histopathology Vol.38,nº12 (2023)

Permanent URI for this collection

https://hdl.handle.net/10201/134253

Browse

Now showing 1 - 12 of 12

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
Mesenchymal stem cell-derived microRNAs: friends or foes of tumor cells?
(Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2023) Harrell, Carl Randall; Djonov, Valentin; Volarevic, Vladislav
Mesenchymal stem cell (MSC)-dependent biological effects in the tumor microenvironment mainly rely on the activity of MSC-sourced microRNAs (MSCmiRNAs) which modulate protein synthesis in target tumor cells, endothelial cells and tumor-infiltrated immune cells, regulating their phenotype and function. Several MSC-sourced miRNAs (miR-221, miR-23b, miR-21-5p, miR-222/223, miR-15a miR-424, miR-30b, miR-30c) possess tumor-promoting properties and are able to enhance viability, invasiveness and metastatic potential of malignant cells, induce proliferation and sprouting of tumor endothelial cells and suppress effector functions of cytotoxic tumor-infiltrated immune cells, crucially contributing to the rapid growth and progression of tumor tissue. On the contrary, MSCs also produce “anti-tumorigenic” miRNAs (miR-100, miR222-3p, miR-146b miR-302a, miR-338-5p, miR-100-5p and miR-1246) which suppress tumor growth and progression by: up-regulating expression of chemoresistance-related genes in tumor cells, by suppressing neo-angiogenesis and by inducing generation of tumorotoxic phenotypes in tumor-infiltrated lymphocytes. In this review article, we summarize the current knowledge about molecular mechanisms that are responsible for MSC-miRNA-dependent alterations of intracellular signaling in tumor and immune cells and we discuss different insights regarding the therapeutic potential of MSC-derived miRNAs in cancer treatment.
Open Access
Clinicopathological features and genomic analysis of bronchiolar adenoma
(Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2023) Bo, Jiaqi; Chen, Xue; Zhang, TingTing; Zhu, Xuyou; Zhang, Long; Liu, Yuting; Zhang, Haoyang; Wu, Caixia; Mou, Shunyan; Yi, Xianghua; Rui, Weiwei; Zeng, Yu
Background. Bronchiolar adenoma (BA) is a rare tumor of the bronchioles with a double-layer structure, including the basal cell layer and the superficial cell layer, and it has a good prognosis. However, the concept of a putative variant of BA has been proposed in the recent literature. Methods. Data on 17 cases of BA were collected from our center. The clinical data, morphology, immunophenotype, and molecular changes were retrospectively analyzed. We also collected the molecular changes in BA reported in the previous literature and summarized the putative driver mutations of BA. Results. Out of 17 BAs, 13 were classic cases with a double-layer structure, including 9 proximal-type and 4 distal-type BAs. Of note, we also identified 3 cases that lacked a continuous basal cell layer, including 2 cases of mixed-type BA with monolayered lesions (basal cells were undetected in some areas) and 1 case of a monolayered BA-like lesion (basal cells were completely undetected). The immunohistochemical findings of monolayer cell lesions were closer to those of minimally invasive adenocarcinoma. We also found one case in which BA transformed into invasive adenocarcinoma accompanied by mutations in the TP53, JAK2, NF1 and RB1 genes. Combined with the previous literature, the most common putative driver gene mutations in 62 BA lesions were EGFR (25/62; 41.0%) and BRAF (21/62; 34.4%). Conclusion. Typical BA has a double-layer cell structure; however, there is also a putative variant of BA, which has a monolayer cell structure and lacks the basal cell layer. Transformation from BA into invasive adenocarcinoma is unusual but can occur
Open Access
Protein atlas of fibroblast specific protein 1 (FSP1)/S100A4
(Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2023) Fendt, Bettina Marturet; Hirschmann, Astrid; Bruns, Malgorzata; Camarillo Retamosa, Eva; Ospelt, Caroline; Vogetseder, Alexander
Fibroblast specific protein 1 (FSP1)/S100A4 is a calcium binding protein which has been linked to epithelial-mesenchymal transition, tissue fibrosis, pulmonary vascular disease, metastatic tumour development, increased tumour cell motility and invasiveness. This protein is reported to be also expressed in newly formed and differentiated fibroblasts and has been used in various studies to demonstrate epithelial-mesenchymal transition (EMT). We aimed to characterize S100A4 positive cells in different human tissue compartments, with the focus on fibroblasts/myofibroblast. We found S100A4 expression in a wide range of cells. Fibroblasts/myofibroblasts showed a broad spectrum of staining intensity, ranging from negative to strong expression of S100A4, with the strongest expression in smooth muscle actin positive myofibroblasts. Cells of haematopoietic lineage, namely CD4 and CD8 positive T-lymphocytes, but not Blymphocytes expressed S100A4. All investigated monocytes, macrophages and specialised histiocytes were positive for S100A4. Even some epithelial cells of the kidney and bladder were positive for S100A4. Expression was also found in the vasculature. Here, cells of the subendothelial space, tunica adventitia and some smooth muscle cells of the tunica media were positive for S100A4. In summary, S100A4 is expressed in various cell types of different lineage and is not, as originally believed, specific for fibroblasts (FSP). Results attained under the premise of specificity of FSP1/S100A4 for fibroblasts, like the founding research on EMT type 2 in kidney and liver, therefore need to be reinterpreted.
Open Access
The combination of the low immunohistochemical expression of peroxiredoxin 4 and perilipin 2 predicts longer survival in pancreatic ductal adenocarcinoma with peroxiredoxin 4 possibly playing a main role
(Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2023) Han, Jia; Itoh, Tohru; Shioya, Akihiro; Sakurai, Masaru; Oyama, Takeru; Kumagai, Motona; Takamura, Hiroyuki; Okuro, Masashi; Mukai, Tsuyoshi; Hidekazu, Kitakata; Inagaki, Masaru; Higashi, Michiyo; Guo, Xin; Yamada, Sohsuke
Pancreatic ductal adenocarcinoma (PDAC) is a fatal disease with poor prognosis. Therefore, indicators that can be used for the early prediction of the prognosis of PDAC are needed. Peroxiredoxin (PRDX) 4 is a secretion-type antioxidant enzyme located in the cytoplasmic endoplasmic reticulum. Recent studies have reported that it is closely related to the development and prognosis of many types of cancer. Perilipin (PLIN) 2 is a lipid droplet coating protein. The high expression of PLIN2 is known to be an indicator of some types of cancer and oxidative stress management. It is highly suggestive of the interplay between PRDX4 and PLIN2 to some degree. In this study, we collected 101 patients’ clinical data and paraffin-embedded specimens with PDAC and analyzed them with immunohistochemical staining of PRDX4 and PLIN2. We found that the low expression of PRDX4 predicts longer survival and a better clinical condition in PDAC patients. Moreover, when the low expression of PRDX4 is combined with the low expression of PLIN2, the 3-year survival is significantly improved. Univariate and multivariate Cox proportional hazard analyses showed that the PRDX4 expression in PDAC was an independent prognostic factor for survival. Taken together, between PRDX4 and PLIN2, PRDX4 plays a main role in prognosis and has the potential to become a clinical prognostic indicator of PDAC.
Open Access
Long noncoding RNA FTX promotes epithelial-mesenchymal transition of epithelial ovarian cancer through modulating miR-7515/TPD52 and activating Met/Akt/mTOR
(Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2023) Li, Yong; Zhu, Xinghua; Zhang, Can; Yin, Yi; Chen, Lei; Liu, Yushan; He, Aiqin; Xia, Fei
Overexpressed long noncoding RNA FTX is associated with low survival rate of epithelial ovarian cancer (EOC) patients, and enhances tumor infiltration. Thus, we aim to illuminate the undefined underlying mechanisms. Real-time quantitative polymerase chain reaction was applied to detect the expressions of FTX, miR-7515, miR-342-3p, miR-940, miR-150-5p, miR205-5p and tumor protein D52 (TPD52). Cell counting kit-8 and transwell assays were utilized to explore the cell viability, migration or invasion of EOC cells. Western blot was conducted to measure the expressions of E-cadherin, N-cadherin, Met, phosphorylated (p)-Met, Akt, p-Akt, mTOR and p-mTOR. LncBase and TargetScan predicted the binding of miR-7515 with FTX, and the binding of TPD52 with miR-7515, respectively. The two bindings were further validated by dual luciferase reporter assay. As a result, FTX sponged miR-7515 and miR-7515 targeted to TPD52. FTX was overexpressed in four EOC cell lines. Overexpressed FTX enhanced the cell viability, migration or invasion of EOC cells, elevated N-cadherin and TPD52 expressions, phosphorylated Met/Akt/mTOR, and inhibited Ecadherin expression. All these influences were subsequently reversed by miR-7515 mimic. Collectively, FTX regulates miR-7515/TPD52 to facilitate the migration, invasion or epithelial-mesenchymal transition of EOC through activating Met/Akt/mTOR signaling pathway.
Open Access
MiR-5195-3p functions as a tumor suppressor by targeting RHBDD1 in ovarian cancer
(Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2023) Wang, Zhanyu; Zhang, Xiaoping; Liu, Yongying; Shi, Xiaoyan; Li, Lijun; Jia, Yun; Wu, Fangfang; Cui, Haosen; Li, Liang
Background. Recent studies have reported the tumor suppressive role of miR-5195-3p in the progression of several cancers, but the potential roles of miR-5195-3p in ovarian cancer (OC) remain largely unknown. Methods. We first analyzed the expression levels of miR-5195-3p in 83 pairs of human OC tissues and adjacent specimens by reverse transcription-quantitative PCR. The correlation of miR-5195-3p/rhomboid domain containing 1 (RHBDD1) and clinicopathological parameters was analyzed by chi-square test. The prognostic value of miR-5195-3p was evaluated by Kaplan-Meier method Cox proportional hazards models. The effects of miR-5195-3p on cell proliferation, cell cycle distribution, migration and invasion were examined by CCK-8 assay, colony formation assay, flow cytometry and transwell assay. Tumor forming was evaluated by nude mice model in vivo. The association between miR-5195-3p and RHBDD1 was verified by luciferase reporter assay. Results. We observed that miR-5195-3p level was remarkably reduced in OC tissues as compared to adjacent tissues. The expression of miR-5195-3p was associated with FIGO stage, depth of invasion and poor survival prognosis in OC patients. Overexpression of miR-5195-3p significantly suppressed cell proliferation, cell cycle G1/S transition, migration and invasion in OC cell lines (SKOV-3 and OVCAR3), while knockdown of miR-5195-3p obtained the opposite results. We further confirmed miR-5195-3p as a negative posttranscriptional modulator of RHBDD1. RHBDD1 expression was upregulated in OC tissues compared with adjacent tissues, which was inversely correlated with miR-5195-3p expression. The expression of RHBDD1 was associated with FIGO stage and distant metastasis. RHBDD1 overexpression reversed the suppressive role of miR-5195-3p on OC cell proliferation, migration and invasion. Consistent with the in vitro results, miR-51953p overexpression decreased the growth of subcutaneously inoculated tumors in nude mice. Conclusions. Taken together, the present results indicated that miR-5195-3p acts a tumor suppressor by targeting RHBDD1 in OC.
Open Access
Transcription factor ZNF488 accelerates cervical cancer progression through regulating the MEK/ERK signaling pathway
(Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2023) Weng, Kena; Li, Lu; Zhou, Haiping
Cervical cancer (CC) is one of the most common gynecological malignancies worldwide. Zinc Finger Protein 488 (ZNF488) has been identified as an oncogene in nasopharyngeal carcinoma. However, its biological role and potential mechanism in CC remain to be elucidated. In the present study, upregulation of ZNF488 expression in human CC tissues was found in clinical samples and analyzed in The Cancer Genome Atlas (TCGA) dataset, which was associated with clinical staging and lymph node metastasis. Quantitative real time polymerase chain reaction (PCR) and western blot assays indicated that the expression of ZNF488 was up-regulated in CC cells. Cell colony formation and cell cycle analysis assays suggested that ZNF488 promoted CC cell proliferation and cycle progression. Knockdown of ZNF488 inhibited tumor growth of xenograft tumor mice in vivo, in agreement with the levels of ZNF488 and Ki-67. Moreover, transwell and western assays demonstrated that ZNF488 enhanced CC cell migration and invasion. Additionally, knockdown of ZNF488 also inhibited lung metastasis of CC cells in vivo. Further mechanism analysis implied that ZNF488 promoted the MEK/ERK signaling pathway. ERK inhibitor PD98059 significantly weakened the proliferation and epithelialmesenchymal transformation (EMT) promotion effect of ZNF488. Collectively, ZNF488 exerts its oncogene function partially through modulating MEK/ERK signaling pathway in CC, indicating that ZNF488 may provide a promising therapeutic target for the treatment of CC.
Open Access
NCK1-AS1 promotes the proliferation, migration, invasion, and EMT of non-small cell lung cancer by regulating the miR-361-5p/ADAM10 axis
(Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2023) Wu, Bingchen; Wang, Zizong; Xu, Hanlin; Chu, Xiangyang; Jiang, Qiwen
Lung cancer, one of the most frequently diagnosed cancers, causes a huge number of mortalities globally. Among lung cancers, non-small cell lung cancer (NSCLC) is the most recorded. Despite accumulating research, the molecular basis of NSCLC progression remains poorly known. Therefore, we aim to assess the function of NCK1-AS1 in NSCLC and elucidate the molecular mechanism. Firstly, we quantified the NCK1-AS1 level in tumors and adjacent healthy tissues. NCK1-AS1 was significantly upregulated in NSCLC tumors, which was associated with poor prognosis in patients. Silencing NCK1-AS1 significantly inhibited the proliferation, migration, and invasion, as well as the EMT of NSCLC cell lines. Starbase bioinformatic prediction revealed that NCK1AS1 targets miR-361-5p which acts to regulate ADAM10 gene expression. Our result showed that NCK1-AS1 upregulation markedly reduced miR-361-5p mRNA expression, while increasing ADAM10 expression. For the first time, we demonstrated that NCK1-AS1 regulates the miR-361-5p/ADAM10 axis, thereby promoting NSCLC progression. NCK1-AS1 might be developed as a therapeutic target for treating NSCLC.
Open Access
LINC01123 acts as an oncogenic driver in lung adenocarcinoma by regulating the miR-4766-5p/PYCR1 axis
(Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2023) Wang, Hong; He, Dongsheng
Background. Lung adenocarcinoma remains one of the most significant threats to human life as it involves multiple etiologies, including alteration of oncogenes or tumor-inhibitory genes. Long non-coding RNAs (lncRNAs) have been reported to have both cancer promoting and cancer inhibiting effects. In this work, we investigated the function and mechanism of lncRNA LINC01123 in lung adenocarcinoma. Methods. The expression of LINC01123, miR-47665p, and PYCR1 (pyrroline-5-carboxylate reductase 1) mRNA was analyzed by RT-qPCR. The protein expression levels of PYCR1 and the apoptosis-related proteins (Bax and Bcl-2) were determined by western blotting. Cell proliferation and migration were determined by CCK-8 and wound-healing assays, respectively. Tumor growth in nude mice and Ki67 immunohistochemical staining were used to determine the in vivo role of LINC01123. The putative binding relationships miR-4766-5p has with LINC01123 and PYCR1, which had been identified by analysis of public databases, were validated through RIP and dualluciferase reporter assays. Results. LINC01123 and PYCR1 overexpression and miR-4766-5p downregulation were shown to occur in lung adenocarcinoma samples. LINC01123 depletion repressed lung adenocarcinoma cell growth and migration and blocked the development of solid tumors in an animal model. Moreover, LINC01123 bound directly to miR-4766-5p, the downregulation of which attenuated the anticancer effects of LINC01123 depletion in lung adenocarcinoma cells. MiR-4766-5p directly targeted downstream PYCR1 to suppress PYCR1 expression. The repressive effects of PYCR1 knockdown on the migration and proliferation of lung adenocarcinoma cells were also partly abolished by miR-4766-5p downregulation. Conclusion. Downregulation of LINC01123 represses lung adenocarcinoma progression. This suggests that LINC01123 functions as an oncogenic driver in lung adenocarcinoma by controlling the miR4766-5p/PYCR1 axis.
Open Access
Potential pitfalls in reporting non- neoplastic gastrointestinal mucosal biopsies
(Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2023) Al Qudah, Mohammad; Murshed, Khaled; Haddad, Husam K.; Haboubi, Najib
Biopsies taken from the gastrointestinal tract (GIT) comprise a significant percentage of the pathologists’ routine work. The variable histology and normal components of each organ along the GIT, as well as the different ways of responding to injury among these organs, can cause morphological changes that could result in potential diagnostic pitfalls. Herein, we review the pathological conditions of the GIT that could cause these diagnostic pitfalls. Our aim was to increase awareness among pathologists and trainees regarding these conditions and provide a pragmatic approach to prevent them and achieve a correct diagnosis.
Open Access
Hsa_circ_0070440 promotes lung adenocarcinoma progression by SLC7A11-mediated-ferroptosis
(Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2023) Zhao, Yong; Cui, Qichen; Shen, Jian; Shen, Weihong; Weng, Yuan
Background. Circular RNA (circRNA) has recently emerged as having a key role in cancer initiation and progression. A prior study exhibited that hsa_circ_0070440 (circ_0070440) was significantly upregulated in lung cancer cells, but the role and molecular mechanism of circ_0070440 during lung adenocarcinoma (LUAD) development remain unclear. Methods. Quantitative real-time polymerase chain reaction (qRT-PCR), Reverse transcription-PCR (RTPCR), RNase R digestion, and Nuclear/cytoplasmic fractionation assay were employed to validate circ_0070440. Proliferation, apoptosis, viability, and ferrous iron level were measured by colony formation, 5-Ethynyl-2'-deoxyuridine (EdU), Annexin V-FITC/PI double staining, Cell Counting Kit-8 (CCK-8), and iron assay in LUAD cells. A xenograft mouse model was used for tumor growth in vivo. Western blot (WB) and immunohistochemistry (IHC) assays were utilized to determine the expression of solute carrier family 7 member 11 (SLC7A11), c-myc, and bcl-xL. The interactions between the circ_0070440/SLC7A11 axis and miR-485-5p were verified by RNA pull-down assay and dual-luciferase reporter assay. Results. Circ_0070440 was significantly upregulated in LUAD cells. Knockdown of circ_0070440 inhibited growth and promoted both apoptosis and ferroptosis of LUAD cells. Moreover, our results showed that circ_0070440 contributed to malignant progression and suppressed ferroptosis of LUAD by sponging miR485-5p and upregulating SLC7A11 expression. Furthermore, circ_0070440 and SLC7A11 levels were up-regulated, and the miR-485-5p level was more downregulated in the tumor tissues than in normal tissues of LUAD patients. Conclusion. Circ_0070440 modulated LUAD malignant progression and ferroptosis via targeting SLC7A11, implying a significant role of the circ_0070440/miR-485-5p/SLC7A11 axis in the diagnosis and treatment of LUAD.

Browse

Browsing Histology and histopathology Vol.38,nº12 (2023) by Issue Date

Results Per Page

Sort Options