Upregulation of microRNA-141 suppresses epithelial-mesenchymal transition and lymph node metastasis in laryngeal cancer through HOXC6-dependent TGF-β signaling pathway

Chen, Li; Sun, Dezhong; Fu, Y J; Yang, Peizhen; Lv, Huaiqing; Gao, Yongli; Zhang, Xiaoyan

doi:10.1016/j.cellsig.2019.109444

Cited by 35 publications

(30 citation statements)

References 39 publications

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“…It has been reported that FAK overexpression is correlated with the invasive potential and lymph node metastasis in HNSCC 21 . TGF-β has also been found to be highly expressed in HNSCC which could increase the survival rate of fibroblasts, enhance cell proliferation and induce lymph node metastasis 22 , 23 . The lysosome is essential to autophagy, it has been mostly relegated to a role secondary to the autophagosome in studies on macroautophagy 24 .…”

Section: Discussionmentioning

confidence: 99%

Development and validation of prognostic index based on autophagy-related genes in patient with head and neck squamous cell carcinoma

et al. 2020

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Head and neck squamous cell carcinoma (HNSCC) is one of the most common cancers worldwide, accounting for almost 50% of all malignancies in developing nations. Autophagy plays a vital role in cancer initiation, malignant progression, and resistance to treatment. However, autophagy-related gene sets have rarely been analyzed in HNSCC. Hence, it is necessary to assess its clinical and pathological significance in a larger cohort of patients with HNSCC. The purpose of this study was to establish a novel autophagy-related prognostic marker for HNSCC. We screened 232 autophagy-related genes (ARGs) and identified 38 differentially expressed ARGs in The Cancer Genome Atlas (TCGA) cohorts. The prognosis-related ARGs signature, established using the univariate and multivariate Cox proportional regression models, consists of 10 ARGs that could divide patients into high-risk and low-risk groups. Survival analysis indicated that patients in the high-risk group had dramatically shorter overall survival compared with their low-risk counterparts. Cox regression analysis further confirmed the independent prognostic value of the autophagy-related signature, and the area under the receiver operating characteristic curve of the combined prognostic model was 0.722. Finally, the efficacy of autophagy-related signature was also validated by an independent cohort from the Gene Expression Omnibus (GEO) database. Collectively, we successfully constructed a novel autophagy-related signature for the prediction of prognosis in patients with HNSCC.

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Section: Discussionmentioning

confidence: 99%

Development and validation of prognostic index based on autophagy-related genes in patient with head and neck squamous cell carcinoma

et al. 2020

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“…Upregulation of miR-495 can reduce high glucose-induced inflammatory, cell differentiation, and extracellular matrix accumulation of human cardiac fibroblasts by blocking the nuclear factor-κB (NF-κB) and TGF-β1/Smad signaling pathways [29]. The blockade of HOXC6-dependent TGF-β signaling pathway is responsible for the suppressed EMT and lymph node metastasis in laryngeal cancer [30]. HOXC6 was found to be abundantly expressed in oral cancer FaDu-PTX cells compared to normal cells [31].…”

Section: Discussionmentioning

confidence: 99%

MicroRNA-495 confers inhibitory effects on cancer stem cells in oral squamous cell carcinoma through the HOXC6-mediated TGF-β signaling pathway

et al. 2020

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Background: Oral squamous cell carcinoma (OSCC) is associated with high morbidity and ranks sixth among malignancies worldwide. Increasing evidence suggests that microRNAs (miRNAs or miRs) play a critical role in regulating cancer stem cells (CSCs), which drive the proliferation and spread of OSCC. Therefore, based on the alteration of aberrantly expressed miR-495 and homeobox C6 (HOXC6) by Gene Expression Omnibus (GEO) analysis, we subsequently explore the potential effect of miR-495 on the progression of CSCs in OSCC. Methods: After the isolation of CSCs from the clinical tissue samples of OSCC patients, the expression of miR-495 and HOXC6 was determined, followed by the validation of the relationship between miR-495 and HOXC6. Subsequently, gain-and loss-function approach was performed to detect the role of miR-495 and HOXC6 in cell proliferation, migration, invasion, cell cycle entry, apoptosis, and epithelial-mesenchymal transition (EMT) of CSCs in OSCC, as well as the tumor growth in vivo. Results: HOXC6 was highly expressed while miR-495 was poorly expressed in OSCC. HOXC6 was verified to be a target gene of miR-495, and miR-495 could inhibit the activation of the TGF-β signaling pathway. CSCs with miR-495 overexpression or HOXC6 silencing exhibited reversed EMT process; reduced abilities of proliferation, migration, and invasion; and promoted cell apoptosis in vitro. Moreover, inhibited tumor growth was observed in vivo after injection with miR-495 agomir or sh-HOXC6. In contrast, the downregulation of miR-495 showed an induced role in the progression of OSCC. Conclusion: These findings suggest that miR-495 may suppress HOXC6 to inhibit EMT, proliferation, migration, and invasion while promoting apoptosis of CSCs in OSCC by inhibiting the TGF-β signaling pathway.

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“…Over recent years, evidence has grown to support the potential regulatory role of miRNAs in the pathological changes that occur in LSCC. For example, mir-141, mir-203, and miR-1469 can influence the progression of LSCC cells via their involvement in epithelial-to-mesenchymal transition (EMT) (7), lymph node metastasis (8), and the p53mediated pathway (9). Other studies have indicated that miR-21, miR-155, miR-192, and miR-375 regulate activation of the NF-kB pathway in LSCC (10).…”

Section: Introductionmentioning

confidence: 99%

Down-Regulation of MiR-181c-5p Promotes Epithelial-to-Mesenchymal Transition in Laryngeal Squamous Cell Carcinoma via Targeting SERPINE1

Fan

et al. 2020

Front. Oncol.

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Laryngeal squamous cell carcinoma (LSCC) arises from the squamous epithelium of the larynx and is associated with a high incidence of cervical lymph node metastasis. MicroRNAs (miRNAs) play a crucial role in the epigenetic regulation of cellular biological processes, including cancer metastasis. However, the molecular mechanisms of specific miRNAs responsible for LSCC metastasis and their clinical significance have yet to be fully elucidated. In this study, LSCC cohort datasets from the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) were downloaded and examined by comprehensive bioinformatics analysis, which revealed that upregulation of mRNA SERPINE1 and downregulation of miR-181c-5p were associated with unfavorable overall survival. Our analysis showed that SERPINE1 expression negatively correlated with the expression level of miR-181c-5p in our LSCC patient samples. Silencing of miR-181c-5p expression promoted cell migration and invasion in cell lines, whereas the overexpression of miR-181c-5p suppressed cell migration and epithelial-to-mesenchymal transition (EMT) through the downregulation of SERPINE1. Further analysis showed that the enhancement effect on EMT and metastasis induced by silencing miR-181c-5p could be rescued through knockdown of SERPINE1 expression in vitro. Collectively, our findings indicated that miR-181c-5p acted as an EMT suppressor miRNA by downregulation of SERPINE1 in LSCC and offers novel strategies for the prevention of metastasis in LSCC.

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Upregulation of microRNA-141 suppresses epithelial-mesenchymal transition and lymph node metastasis in laryngeal cancer through HOXC6-dependent TGF-β signaling pathway

Cited by 35 publications

References 39 publications

Development and validation of prognostic index based on autophagy-related genes in patient with head and neck squamous cell carcinoma

Development and validation of prognostic index based on autophagy-related genes in patient with head and neck squamous cell carcinoma

MicroRNA-495 confers inhibitory effects on cancer stem cells in oral squamous cell carcinoma through the HOXC6-mediated TGF-β signaling pathway

Down-Regulation of MiR-181c-5p Promotes Epithelial-to-Mesenchymal Transition in Laryngeal Squamous Cell Carcinoma via Targeting SERPINE1

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