MicroRNA-7 inhibits cell proliferation, migration and invasion in human non-small cell lung cancer cells by targeting FAK through ERK/MAPK signaling pathway

Cao, Qi; Mao, Zhengdao; Shi, Yujia; Chen, Yi; Sun, Yun-Fan; Zhang, Qian; Song, Lei; Peng, Liping

doi:10.18632/oncotarget.12684

Cited by 73 publications

(56 citation statements)

References 33 publications

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“…In addition, the Erk signaling pathway has been shown to be frequently activated in numerous kinds of human cancers [43][44][45]. Aberrant activation of phosphorylated Erk1/2 induced by miRNAs has been observed in lung cancer [45][46][47]. Recent reports point out that miR-379 acts as a tumor [45], miR-7 inhibits the activation of ERK/MAPK signaling pathway by down-regulating FAK expression [46], and miR-622 overexpression decreases invasion in lung tumor cells by inhibiting HIF-1alpha via inactivation of ERK signaling in A549 cell [47].…”

Section: Discussionmentioning

confidence: 99%

“…Aberrant activation of phosphorylated Erk1/2 induced by miRNAs has been observed in lung cancer [45][46][47]. Recent reports point out that miR-379 acts as a tumor [45], miR-7 inhibits the activation of ERK/MAPK signaling pathway by down-regulating FAK expression [46], and miR-622 overexpression decreases invasion in lung tumor cells by inhibiting HIF-1alpha via inactivation of ERK signaling in A549 cell [47]. Consistent with these findings, we found that the p-Erk level was significantly decreased in response to GCNT3 silencing or miR-302b-3p overexpression in XWLC and NCI-H292 cells, suggesting that the effect of the miR-302b-3p/GCNT3 signaling pathway in NSCLC may depend on the activation of p-Erk.…”

Section: Discussionmentioning

confidence: 99%

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Downregulation of N-Acetylglucosaminyltransferase GCNT3 by miR-302b-3p Decreases Non-Small Cell Lung Cancer (NSCLC) Cell Proliferation, Migration and Invasion

Ran

Guo

et al. 2018

Cell Physiol Biochem

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Background/Aims: GCNT3 is a member of N-acetylglucosaminyltransferase family involved with mucin biosynthesis. GCNT3 aberrant expression is known to promote the progression of several human cancers. However, its role in tumorigenesis and the progression of non-small cell lung cancer (NSCLC) has not been well-characterized. Our study investigated the functional mechanisms of GCNT3 regulated by microRNAs (miRNAs) in NSCLC. Methods: The differential expression of mRNAs in NSCLC tissues and matched adjacent non-cancerous lung tissues from patients in Xuanwei, Yunnan province, China, was screened via mRNA microarray. The expression of GCNT3 and its correlation with NSCLC progression was measured in 92 paired tumor tissues and adjacent normal tissues. The functions of GCNT3 in NSCLC cells and its underlying mechanisms were measured using siRNA and GCNT3-expression vectors. The miRNA immunoprecipitation (miRIP) method was used to identify the miRNAs targeting GCNT3. The protein were measured using western blot assay, and the mRNAs were measured by quantitative real-time PCR (qRT-PCR) assay. Cell proliferation was measured using Cell Counting Kit-8 (CCK-8) and a colony forming assays; cell migration and invasion assays were performed using 24-well Transwell chambers with 8-μm pores filter, and analyses of the cell cycle and apoptosis were performed via flow cytometric analysis. The dual luciferase reporter assay was performed to confirm whether GCNT3 gene was a direct target of miR-302b-3p. Results: GCNT3 was found to be highly expressed in both NSCLC tissues and cell lines, and higher expression correlated significantly with advanced tumor-node-metastasis (TNM) stage, positive lymph node metastasis, and poor overall survival. Knockdown of GCNT3 inhibited the proliferation, migration and invasion ability of NSCLC cells, while overexpression facilitated these activities. Further mechanistic experiments using miRIP and dual luciferase reporter assays revealed that GCNT3 was a direct target of miR-302b-3p. Low expression of miR-302b-3p was found in NSCLC cells and negatively correlated with GCNT3 levels, while miR-302b-3p overexpression inhibited the proliferation, migration and invasion of NSCLC cells. Co-transfection with miR-302b-3p and the expression vector of GCNT3 abrogated the effects of mir-302b-3p, confirming that miR-302b-3p inhibited NSCLC progression by targeting GCNT3. Western blotting revealed that E-cadherin, N-cadherin, vimentin, p-Erk and cyclin D1 were downstream molecules of miR-302b-3p/GCNT3 pathway. Conclusion: miR-302b-3p/GCNT3 axis regulated cell proliferation, migration, and invasion by activating the Erk signaling pathway and epithelial-mesenchymal transition (EMT), which was identified as a potential therapeutic target for NSCLC.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Downregulation of N-Acetylglucosaminyltransferase GCNT3 by miR-302b-3p Decreases Non-Small Cell Lung Cancer (NSCLC) Cell Proliferation, Migration and Invasion

Ran

Guo

et al. 2018

Cell Physiol Biochem

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“…Furthermore, miR‐7 also participated in the pathogenesis that initiated the development of assorted disorders through acting on the downstream pathways. To be specific, miR‐7 could affect proliferation and migration of NSCLC cells by modulation of ERK/MAPK signalling or mediation of TLR9 signalling 16, 17. The miR‐7/NF‐κB signalling axis also mattered for its modulating the metastatic conditions of gastric cancer cells, so this axis might also be responsible for the aetiology of additional cancers, such as NSCLC 18, 19, 20.…”

Section: Introductionmentioning

confidence: 99%

CiRS‐7 targeting miR‐7 modulates the progression of non‐small cell lung cancer in a manner dependent on NF‐κB signalling

Zhang

et al. 2018

J Cellular Molecular Medi

110

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The purpose of this study was to figure out the effect of ciRS‐7/miR‐7/NF‐κB axis on the development of non‐small cell lung cancer (NSCLC). In response, the expressions of ciRS‐7, miR‐7 and NF‐κB subunit (ie RELA) within NSCLC tissues and cell lines were determined with real‐time polymerase chain reaction (RT‐PCR) and Western blot. Moreover, the NSCLC cells were transfected with pcDNA3‐ciRS‐7‐ir, pcDNA3‐ciRS‐7, miR‐NC and miR‐7 mimic. Furthermore, the targeted relationships between ciRS‐7 and miR‐7, as well as between miR‐7 and RELA, were confirmed by luciferase reporter assay. The proliferation, migration and apoptosis of NSCLC cells were, successively, measured using CCK‐8 assay, wound‐healing assay and flow cytometry test. Consequently, ciRS‐7, miR‐7, histopathological grade, lymph node metastasis and histopathological stage could independently predict the prognosis of patients with NSCLC (all P < .05). Moreover, remarkably up‐regulated ciRS‐7 and RELA expressions, as along with down‐regulated miR‐7 expressions, were found within NSCLC tissues and cells in comparison with normal ones (P < .05). Besides, overexpressed ciRS‐7 and underexpressed miR‐7 were correlated with increased proliferation, migration and invasion, yet reduced apoptosis rate of NSCLC cells (P < .05). More than that, ciRS‐7 specifically targeted miR‐7 to reduce its expressions (P < .05). Ultimately, the NSCLC cells within miR‐7 + RELA group were observed with superior proliferative, migratory and invasive capabilities than those within miR‐7 group (P < .05), and RELA expression was also significantly modified by both ciRS‐7 and miR‐7 (P < .05). In conclusion, the ciRS‐7/miR‐7/NF‐kB axis could exert pronounced impacts on the proliferation, migration, invasion and apoptosis of NSCLC cells.

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“…Zhao’ et al showed that miR-7 enhances cytotoxicity induced by gefitinib in NSCLC via inhibiting the EGFR and IGF1R signalling pathways [10]. Also, it was reported that miR-7 inhibits cell proliferation, migration and invasion in human non-small cell lung cancer cells by targeting FAK through ERK/MAPK signaling pathway [11]. However, the clinicopathological and prognostic significance of miR-7 in human LA and its roles in regulation of CDDP resistance of LA cells are unclear.…”

Section: Introductionmentioning

confidence: 99%

Prognostic Significance of microRNA-7 and its Roles in the Regulation of Cisplatin Resistance in Lung Adenocarcinoma

Cheng

Shen

et al. 2017

Cell Physiol Biochem

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Background: Previously, microRNA (miR)-7 has been reported to function as a tumor suppressor in human cancers, but the correlations of miR-7 expression with prognosis and cisplatin (CDDP) resistance in lung adenocarcinoma (LA) are unclear. Here, our aim is to determine the prognostic significance of miR-7 and its roles in the regulation of CDDP resistance in LA. Methods: Quantitative real-time PCR (qRT-PCR) assay was performed to determine miR-7 expression in 108 paired of LA tissues and analyze its correlations with clinicopathological factors of patients. The patient survival data were collected retrospectively by Kaplan-Meier analyses, and multivariate analysis was performed using the Cox proportional hazards model to determine the prognostic significance of miR-7 expression. The effects of miR-7 expression on the chemosensitivity of LA cells to CDDP and its possible mechanisms were evaluated by MTT, flow cytometry, Western blot and luciferase assays. Results: It was observed that the relative expression level of miR-7 in LA tissues was significantly lower than that in the adjacent normal tissues and low miR-7 expression level was closely associated with poorer tumor differentiation, advanced pathological T-factor, higher incidence of lymph node metastasis and advanced p-TNM stage. Also, patients with low miR-7 expression showed a shorter overall survival than those with high miR-7 expression, and multivariate analysis indicated that status of miR-7 expression was an independent molecular biomarker for predicting the overall survival (OS) of LA patients. In addition, upregulation of miR-7 increases the sensitivity of LA cells to CDDP via induction of apoptosis by targeting Bcl-2. Conclusions: Our finding for the first time demonstrates that low miR-7 expression may be an independent poor prognostic factor and targeting miR-7 may be a potential strategy for the reversal of CDDP resistance in LA.

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MicroRNA-7 inhibits cell proliferation, migration and invasion in human non-small cell lung cancer cells by targeting FAK through ERK/MAPK signaling pathway

Cited by 73 publications

References 33 publications

Downregulation of N-Acetylglucosaminyltransferase GCNT3 by miR-302b-3p Decreases Non-Small Cell Lung Cancer (NSCLC) Cell Proliferation, Migration and Invasion

Downregulation of N-Acetylglucosaminyltransferase GCNT3 by miR-302b-3p Decreases Non-Small Cell Lung Cancer (NSCLC) Cell Proliferation, Migration and Invasion

CiRS‐7 targeting miR‐7 modulates the progression of non‐small cell lung cancer in a manner dependent on NF‐κB signalling

Prognostic Significance of microRNA-7 and its Roles in the Regulation of Cisplatin Resistance in Lung Adenocarcinoma

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