DigitalUM :: Browsing by Subject "Non-small cell lung cancer"

Browsing by Subject "Non-small cell lung cancer"

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Open Access
CBP-mediated FOXO4 acetylation facilitates postmenopausal osteoporosis (PMO) progression through the inhibition of the Wnt/β-catenin signaling pathway
(Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2024) Huang, Qiubo; Wang, Jiang
FOXO4 was previously identified as a potential biomarker and therapeutic target for postmenopausal osteoporosis (PMO) using bioinformatic analysis, but its specific function and molecular mechanism in the progression of osteoporosis was not reported. The current study was designed to investigate the biological function and underlying mechanism of FOXO4 in PMO. Our results showed that FOXO4 expression was significantly upregulated in the serum samples of PMO patients, which was also negatively correlated with the expression of osteogenesis genes (OCN and ALP). In addition, FOXO4 depletion alleviated osteoporosis by facilitating osteogenic differentiation and inhibiting adipogenic differentiation in human bone marrow mesenchymal stem cells (hBMSCs). Overexpression of FOXO4 exerted the opposite effects on the osteogenic/adipogenic differentiation in hBMSCs. Moreover, FOXO4 knockdown activated the Wnt/β-catenin signaling whereas the inhibition of Wnt/β-catenin signaling overturned the effects of FOXO4 deficiency on osteoporosis. Furthermore, FOXO4 upregulation in PMO was caused by CBP-induced acetylation. In summary, our data demonstrated that FOXO4 was a potent biomarker for PMO and mediated the balance between osteogenesis and adipogenesis in hBMSCs by regulating Wnt/β-catenin signaling
Open Access
Circ_0007385 promotes the proliferation and inhibits the apoptosis of non-small cell lung cancer cells via miR-337-3p-dependent regulation of LMO3
(Universidad de Murcia. Departamento de Biología Celular e Histología, 2023) Wei, Mingchao; Yin, Rongjiang; Qu, Li; Tang, Jian
Background. This study intended to analyze the expression characteristic, functions and underlying mechanism of circular RNA_0007385 (circ_0007385) in non-small cell lung cancer (NSCLC). Methods and Results. RNA and protein expression was examined by real-time quantitative polymerase chain reaction (RT-qPCR) and Western blot assay. Cell counting kit 8 (CCK8) assay, colony formation assay, 5- Ethynyl-2’-deoxyuridine (EdU) assay and flow cytometry were applied to analyze cell proliferation ability. Flow cytometry was also conducted to assess cell apoptosis. Dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay were performed to verify the predicted target relationships. Xenograft tumor model was utilized to analyze the function of circ_0007385 in vivo, and immunohistochemistry (IHC) assay was used to analyze protein expression in xenograft tumor tissues. Circ_0007385 expression was notably enhanced in NSCLC tissues and cell lines. Circ_0007385 facilitated the proliferation but suppressed the apoptosis of NSCLC cells. Circ_0007385 acted as a sponge for microRNA-337-3p (miR-337-3p), and circ_0007385 overexpression-mediated effects were largely overturned by the overexpression of miR-337-3p in NSCLC cells. MiR-337-3p interacted with the 3’ untranslated region (3’UTR) of LIM-only protein 3 (LMO3). Circ_0007385 up-regulated LMO3 level by absorbing miR-337-3p in NSCLC cells. LMO3 overexpression largely reversed miR-337-3p overexpression-induced influences in NSCLC cells. Circ_0007385 knockdown significantly restrained the growth of xenograft tumors in vivo. Conclusion. Circ_0007385 promoted the proliferation ability and inhibited the apoptosis of NSCLC cells by binding to miR-337-3p to induce LMO3 expression.
Open Access
Circ_SATB2 knockdown inhibits the tumorigenesis of non-small cell lung cancer via miR-760/KIF2A axis
(Universidad de Murcia. Departamento de Biología Celular e Histología, 2023) Zheng, Pengchao; Jiang, Jianhua; Li, Lei; Wei, Liang; Li, Jie; Jin, Ling
Purpose. This study was aimed at exploring the function and underlying mechanism of circ_SATB2 in non-small cell lung cancer (NSCLC). Methods. The levels of circ_SATB2, microRNA-760 (miR-760) and Kinesin family member 2a (KIF2A) were determined using quantitative real-time polymerase chain reaction or western blot assay. The proliferation was detected using MTT and colony formation assays. Cell cycle and apoptosis were evaluated by flow cytometry. Transwell assay for migration and invasion and western blot for metastasis-associated proteins were conducted. Dual-luciferase reporter assay was used to analyze the interaction between miR-760 and circ_SATB2 or KIF2A. The effect of circ_SATB2 on NSCLC tumor growth in vivo was studied by xenograft mice model. Results. Circ_SATB2 was upregulated in NSCLC tissues and cells. Circ_SATB2 knockdown caused inhibitory effects on NSCLC cell proliferation and metastasis but accelerated apoptosis. Circ_SATB2 served as a sponge of miR-760 to act in the development of NSCLC. Moreover, miR-760 could target KIF2A, and KIF2A expression was positively regulated by circ_SATB2. Furthermore, KIF2A overexpression neutralized miR-760-mediated inhibition effects on NSCLC cell progression. Besides, circ_SATB2 enhanced NSCLC tumorigenesis by targeting miR760/KIF2A axis in vivo. Conclusion. Circ_SATB2 was highly expressed and participated in the progression of NSCLC through the modulation of the miR-760/KIF2A axis, suggesting that circ_SATB2 might be a potential biomarker for the diagnosis of NSCLC.
Open Access
CircTADA2A Up-regulates MAPK8 by targeting MiR-214-3p and recruiting EIF4A3 to promote the invasion and migration of non-small cell lung cancer cells
(Universidad de Murcia. Departamento de Biología Celular e Histología, 2023) Zhang, Xi; Lei, Guangyan; Zhao, Kun; Zhang, Xinwei; Dang, Chengxue
Background. Non-small cell lung cancer (NSCLC) occupies 87% of all lung cancer cases. Due to delayed diagnosis, the prognosis of NSCLC is unfavorable. To improve the survival of patients with NSCLC, more effective therapeutic targets urgently need to be identified. Recently, circular RNAs (circRNAs) have been revealed to play a crucial role in NSCLC progression. Purpose. This research focused on the influence of circTADA2A on the malignant phenotype of NSCLC cells and its in-depth regulatory mechanisms. Methods. RT-qPCR and western blot assays were done to examine the level of gene/protein of interest. Wound healing and transwell assays were conducted to monitor the migration and invasion of NSCLC cells. Bioinformatics tools and mechanistic assays were utilized to delve into the underlying mechanism of circTADA2A in NSCLC cells. Results. The results demonstrated that circTADA2A presented a high expression in NSCLC. CircTADA2A knockdown was revealed to hamper migration and invasion of NSCLC cells. Mechanistically, circTADA2A elevated MAPK8 expression through sequestering miR214-3p and recruiting EIF4A3. Conclusion. CircTADA2A enhances MAPK8 expression by serving as a miR-214-3p sponge and EIF4A3 decoy, consequently promoting invasion and migration of NSCLC cells.
Open Access
Expression of γ-tubulin in non-small cell lung cancer and effect on patient survival
(Universidad de Murcia. Departamento de Biología Celular e Histología, 2019) Maounis, Nicoletta F.; Dráberová, Eduarda; Trakas, Nikos; Chorti, María; Riga, Dimitra; Tzannis, Kimon; Kanakis, Meletis; Voralu, Kirtanaa; Ellina, Eleni; Mahera, Eleni; Demonakou, Maria; Lioulias, Achilleas; Dráber, Pavel; Katsetos, Christos D.
Introduction. It has been reported that overexpression and altered compartmentalization of γtubulin may contribute to tumorigenesis and tumor aggressiveness in a variety of human malignancies. We have shown that γ-tubulin expression and cellular distribution pattern is also altered in non-small cell lung cancer (NSCLC) (Histol. Histopathol. 2012; 27: 1183- 1194). In the present study we examined the relationship between γ-tubulin expression and patient overall survival (OS). Material and methods. Immunohistochemistry was performed, with well-characterized anti-γ-tubulin antibodies, on 109 formalin-fixed, paraffin-embedded NSCLC specimens (p-TNM stage IIII). γ-Tubulin labeling indexes (LIs) were determined, and the association of γ-tubulin expression with clinicopathological parameters was evaluated. To analyze OS rates according to γ-tubulin LIs, patients were categorized into three groups: those with low (0- 30%), intermediate (31-69%) or high (70-100%) γtubulin LI. Association of clinicopathological parameters and γ-tubulin with survival were examined using univariate and multivariate Cox regression analysis. Results. No statistically significant association was seen between γ-tubulin overexpression and histological type, tumor differentiation, p-TNM stage and adenocarcinoma subtyping. Longer survival was observed in the high γtubulin LI group of patients with p-TNM stages II+III when compared to intermediate or low γ-tubulin LI groups, but the difference was not statistically significant (p=0.066). On the other hand, when combined low and intermediate γ-tubulin LI groups (p-TNM stages II+III) where compared to high γ-tubulin LI group, statistically significant longer survival was observed in high γtubulin group (p=0.021). Conclusion. Our findings suggest that level of γ-tubulin expression may have an impact on patient survival at more advanced NSCLC stages.
Open Access
Extra-meningeal solitary fibrous tumor: an evolving entity with chameleonic morphological diversity, a hallmark molecular alteration and unresolved issues in risk stratification assessment
(Universidad de Murcia. Departamento de Biología Celular e Histología, 2023) Machado, Isidro; Giner, Francisco; Cruz, Julia; Lavernia, Javier; Marhuenda Fluixa, Ana; Claramunt, Reyes; López Guerrero, José Antonio; Navarro, Samuel; Ferrandez, Antonio; Blázquez Bujeda, Álvaro; Ruiz-Sauri, Amparo; Llombart Bosch, Antonio
Solitary fibrous tumor (SFT) is a rare type of mesenchymal lesion with variable clinical presentation in which specific clinicopathologic factors have been related to patient outcome. SFT shares an important morphologic and immunohistochemical overlap with other sarcomas, hence the differential diagnosis is challenging. Although molecular studies provide significant clues, especially in the differential diagnosis with other neoplasms, a thorough hematoxylin and eosin analysis and the integration of phenotypical, clinical, and radiological features remain an essential tool in SFT diagnosis. In this review, we discuss some emerging issues still under debate in SFT.
Open Access
High expression of the phosphoinositide 3-kinase p110γ isoform can predict poor prognosis of non-small cell lung cancer
(Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2022) Jung, Ina; Lee, Hyoun Wook; Roh, Mee Sook; Lee, Jae Seok; Kim, Kisu; Kim, Kyungeun; Kim, Tae Gyu; Nam, Hyun-Yeol
The protein p110γ is an isoform of the catalytic subunit of class I phosphoinositide 3-kinases (PI3Ks). PI3Ks are involved in the regulation of cell survival, growth, proliferation, and migration and have been implicated in the oncogenesis of various cancers. In this study, p110γ expression in non-small cell lung cancer (NSCLC) and its association with clinicopathological factors and patient survival were evaluated. A total of 230 NSCLC tumors were immunohistochemically stained for p110γ. Of these, 174 (75.7%) and 56 (24.3%) were placed in the low and high expression groups, respectively. The positive rate of p110γ was significantly higher in adenocarcinoma than in squamous cell carcinoma (p<0.001). Advanced stage NSCLCs showed higher p110γ expression than those at an early stage (p=0.002). Irrespective of the histological tumor type, the patients with high p110γ expression had significantly worse overall survival than those with low p110γ expression (p=0.004). p110γ expression was an independent poor prognostic factor in the multivariate analysis. Our results suggest that p110γ may be involved in the development and progression of NSCLC, and that p110γ has promising potential as a prognostic factor or novel therapeutic target for NSCLC.
Open Access
High miR-3648 expression and low APC2 expression are associated with shorter survival and tumor progression in NSCLC
(Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2022) Dong, Yongquan; Wu, Biao; Wang, Xiongxiong; Lu, Feijie; Li, Qianjun; Zhao, Qiong
Background. Emerging studies have demonstrated that microRNAs (miRNAs) play crucial roles in the carcinogenesis of many developing human tumors. However, the clinical significance and biological function of microRNA-3648 (miR-3648) in non-small cell lung cancer (NSCLC) have been largely undefined. Methods. The expression of miR-3648 and the mRNA of adenomatous polyposis coli 2 (APC2) in NSCLC tissues and cell lines were analyzed using quantitative real-time RT-PCR. The prognostic value of miR-3648 and APC2 was examined using the KaplanMeier method and Cox regression analyses. Experiments using NSCLC cells were conducted to explore the influences of miR-3648 on tumor cell proliferation, migration and invasion. Result. Increased expression of miR-3648 was observed in NSCLC tissues and cell lines compared with the corresponding controls (all P<0.05). miR-3648 expression was associated with the differentiation, lymph node metastasis and TNM stage (all P<0.05) of NSCLC patients, and high expression of miR-3648 was associated with poor overall survival rate. NSCLC cell proliferation, migration and invasion were significantly enhanced by miR-3648 overexpression. The further luciferase reporter assay and expression results showed that the decreased APC2 might also be a prognostic biomarker, and served as a target of miR-3648 in NSCLC. Conclusion. The findings from the present study indicate that the overexpression of miR-3648 serves as a useful biomarker for the prediction of prognosis in NSCLC, and promotes tumor cell proliferation, migration and invasion. APC2, as another prognosisrelated molecule, may be a target of miR-3648 in NSCLC.
Open Access
Novel PD-L1 mAb HC16 reveals upregulation of PD-L1 in BAC subtype
(Universidad de Murcia. Departamento de Biología Celular e Histología, 2021) Su, Bor Chyuan; Ting, Chen Hung; Lee, Kang Yun; Wu, Sheng Ming; Feng, Po Hao; Chan, Yao Fei; Chen, Jyh Yih
Programmed death-ligand 1 (PD-L1) is an inhibitory transmembrane protein that can prevent autoimmune response. Upregulated PD-L1 serves as a predictive biomarker for patients who may respond well to immune checkpoint therapies. However, variable associations of PD-L1 level with prognoses have been reported. In this study, a short peptide sequence corresponding to PD-L1 amino acids 172-187 (from the extracellular Ig-like C-type domain, and with high predicted antigenicity and hydrophilicity) was used to generate a monoclonal antibody (mAb). The resultant PD-L1 mAb, clone HC16, was examined for binding specificity and reactivity in cancer cell-lines, as assessed by immunocytochemical, immunoblotting, and coimmunoprecipitation. The potential diagnostic and clinical applicability of clone HC16 was further tested using malignant tissue arrays derived from various cancer types analyzed with an automated immunohistochemical (IHC) staining platform. Additionally, tumor samples from patients diagnosed with non-small cell lung cancer (NSCLC) were analyzed by western blotting. Clone HC16 showed obvious staining activity in lung and breast cancer tissues. Interestingly, we observed that PD-L1 level was negatively associated with clinical stage in NSCLC. Strong PD-L1 expression tended to be found in patients diagnosed with bronchioloalveolar carcinoma (BAC). These results demonstrate that clone HC16 harbors good target specificity and is suitable for further development in diagnostic tools to assess PD-L1 expression in human tissues. In addition, our findings also suggest a role for PD-L1 in a non-invasive subtype of lung cancer.
Open Access
Prognostic value of long noncoding RNA LINC00924 in lung adenocarcinoma and its regulatory effect on tumor progression
(Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2024) Zhang, Wenlong; Zhao, Yanan; Jia, Yuanyuan; Bai, Yuansong
Purpose. Long non-coding RNAs (lncRNAs) have been used in the study of tumor biomarkers in recent years. However, the prognostic role of lncRNA LINC00924 (LINC00924) in lung adenocarcinoma (LUAD) has not yet been concluded. Therefore, this study investigates the prognostic value of LINC00924 in LUAD and its regulatory effect on tumor progression. Patients and methods. The LUAD tissues and adjacent normal tissues of 128 subjects were extracted, and the expressions of LINC00924 and miR-196a-5p in tissues and cells were detected by RT-qPCR. The prognostic value of LINC00924 in LUAD patients was obtained by Kaplan-Meier analysis and multivariate Cox regression test. The cell counting kit-8 (CCK-8) and Transwell assay were used to detect the effect of overexpression LINC00924 on LUAD cells. Results. In LUAD tissues and cells, LINC00924 expression was down-regulated and miR-196a-5p expression was up-regulated compared with the normal control group. High expression of LINC00924 inhibited the proliferation level, migration ability and invasion situation of LUAD cells, which was more conducive to the survival and prognosis of LUAD patients. Bioinformatics studies indicated that overexpression of LINC00924 inhibited the development of LUAD by targeting miR-196a-5p, while miR-196a-5p mimic effectively weakened the inhibition.Conclusion. LINC00924 sponges of miR-196a-5p may be considered as a potential prognostic biomarker for LUAD.
Open Access
Prognostic value of mutant p53, Ki-67, and TTF-1 and their correlation with EGFR mutation in patients with non-small cell lung cancer.
(Celular e Histiologia Universidad de Murcia, Departamento de Biologia, 2019) Zhu, Wang-Yu; Hu, Xiao-Fei; Fang, Ke-Xin; Kong, Qiong-Qiong; Cui, Ri; Feng, Hai; He, Jian-Ying; Zhang, Yong-kui; Le, Han-Bo
Introduction. The clinical characteristics of non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) mutation have been well studied. However, the correlation of EGFR mutation with mutant p53, Ki-67, and thyroid transcription factor 1 (TTF-1) and their prognostic value remain indistinct. Material and methods. Clinical and pathological characteristics and overall survival were analysed retrospectively in 523 surgically resected NSCLC patients. The expression levels of p53, Ki-67, and TTF-1 protein were detected by immunohistochemistry, and an amplification refractory mutation system was used to access the status of EGFR mutations. Results. Of 523 patients with surgically resected NSCLC, 210 patients (38.4%) harboured EGFR mutations. Compared to the EGFR wild-type lung cancer, mutated EGFR harboured significantly increased mutant p53-positive or TTF-1-positive tumors (P<0.001 and <0.001, respectively). Former or current smokers, pathological stage and mutant p53-or TTF-1-positive status were independent predictors of EGFR mutation (P=0.001, 0.014, 0.014 and <0.001, respectively). Patients with p53 under expression had significantly better overall survival in the whole cohort and wild-type EGFR cohort (P=0.0010 and 0.0020, respectively) as well as in Ki-67-negative and TTF-1-positive patients (P<0.0001 and 0.0009, and P<0.0001 and 0.0004, respectively). Interestingly, in patients harbouring EGFR mutations, p53-under expression and Ki-67-negative cases still had better survival than positive cases, whereas there was no obvious difference between TTF- 1-negative and TTF-1-positive cases (P=0.0198, 0.0068 and 0.3684, respectively). Finally, in NSCLC patients with wild-type EGFR, positive Ki-67 expression was the independent predictor for the worst survival (P=0.022). Conclusion. The expression levels of mutant p53, Ki-67, and TTF-1 were correlated with EGFR mutation. High expression of mutant p53 and Ki-67 correlated with poor survival in the entire cohort, EGFR mutation or wild-type cohort. In addition, Ki-67 might have an impact on the prognosis for patients with NSCLC with wild-type EGFR.
Open Access
RHCG inhibition promotes the sensitivity of PIK3CA-mutant non-small lung cancer to PI3K inhibitor
(2026) Muqun Wang; Yingying Pang; Haitao Liu; Biología Celular e Histología; Universidad de Murcia, Departamento de Biología Celular e Histología
PIK3CA, the gene encoding the catalytic subunit of the PI3K complex, is significantly amplified and mutated in several cancer forms, including non small cell lung cancer (NSCLC). Although follicular lymphoma and chronic lymphocytic leukemia have been treated clinically with PI3K inhibitors, there are currently no FDA-approved medications targeting PI3K mutations in lung cancer. In this study, by TCGA database analysis, we found that RHCG was highly expressed in PIK3CA-mutated NSCLC and was associated with poor prognosis. Knockdown of RHCG in PIK3CA-mutated NSCLC inhibited cell proliferation and promoted apoptosis, thereby sensitizing cells to PI3K inhibitors. Mechanistically, the knockdown of RHCG acts synergistically with PI3K inhibitors to produce more effective inhibition of AKT and S6RP phosphorylation downstream of PI3K. This finding suggests a potential NSCLC target with PIK3CA mutations.
Open Access
The prognostic impact of tumor-associated macrophages and intra-tumoral apoptosis in non-small cell lung cancer
(F. Hernández y Juan F. Madrid. Universidad de Murcia: Departamento de Biología Celular e Histología, 2014) Becker, Matheus; Müller, Carolina Beatriz; De Bastiani, Marco Antônio; Klamt, Fábio
Summary. Lung cancer is the leading cause of cancerrelated deaths worldwide. Non-small cell lung cancer (NSCLC) accounts for 80% of all lung malignancies. Tumor-associated macrophages (TAM) are abundant components of NSCLC. Although under certain conditions TAM can kill tumor cells, they can also act as tumor promoters secreting a variety of factors that directly stimulate tumor invasion and metastasis. TAM presents two distinct phenotypes: the classically activated (or M1) phenotype, which is highly proinflammatory (phagocytic and cytotoxic), and the alternatively activated (or M2) phenotype, which has anti-inflammatory and pro-tumoral properties. The polarization status of TAM depends on stimulating factors from the tumor microenvironment, and some in vitro evidence implies that the phagocytosis of apoptotic bodies derived from tumoral cells is a key factor in M1/M2 modulation, raising the question of whether the evaluation of the apoptotic index (AI) and macrophage polarization have a prognostic role in NSCLC patient survival. The present article systematically reviewed the published series of clinical data that correlated the AI and/or macrophage densities and polarization status (M1/M2) with the outcome of non-small cell lung cancer patients. Even though an overwhelming body of clinical data support that TAM’s density, micro-anatomical localization, phenotype and intra-tumoral AI are independent predictors of survival time, no study to date has been conducted to evaluate the impact of these parameters altogether in NSCLC patient outcome. Joint analysis of these biologic factors in future studies might reveal their prognostic value in the management of NSCLC cases.

Browsing by Subject "Non-small cell lung cancer"

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