MiR-661 promotes tumor invasion and metastasis by directly inhibiting RB1 in non small cell lung cancer

Feiye Liu,Yanjun Cai,Xiaoxiang Rong,Lu Chen,Rongcheng Luo,Junyi Zhang,Jian Ruan,Dayong Zheng,Peng Zhao,Jinzhang Chen

doi:10.1186/s12943-017-0698-4

Abstract

BackgroundAberrant microRNA expression has been implicated in metastasis of cancers. MiR-661 accelerates proliferation and invasion of breast cancer and ovarian cancer, while impedes that of glioma. Its role in non small cell lung cancer (NSCLC) and underlying mechanism are worthy elucidation.MethodsExpression of miR-661 was measured with real-time PCR in both NSCLC tissues and cell lines. The effects of miR-661 on migration, invasion and metastasis capacity of NSCLC were evaluated using wound healing, transwell assay and animal models. Dual reporter luciferase assay and complementary experiments were performed to validate RB1 as a direct target of miR-661 for participation in the progression of NSCLC.ResultsMiR-661 was upregulated in NSCLC tissues as compared to paired adjacent tissues and associated with shorter overall survival. Furthermore, miR-661 promoted proliferation, migration and metastasis of NSCLC. Then, we identified RB1 as a direct target of miR-661 through which miR-661 affected EMT process and metastasis of NSCLC. RB1 interacted with E2F1 and both could mediate EMT process in NSCLC.ConclusionMiR-661 promotes metastasis of NSCLC through RB/E2F1 signaling and EMT events, thus may serves as a negative prognostic factor and possible target for treatment of NSCLC patient.

Highlights

Aberrant microRNA expression has been implicated in metastasis of cancers
MiR-661 expression was upregulated in non small cell lung cancer (NSCLC) and an indicator for poorer prognosis To measure miR-661 expression in NSCLC tissue, realtime PCR was performed in 50 NSCLC specimens and paired adjacent tissues
MiR-661 expression were significantly correlated with tumor size, lymph node and metastasis status instead of age, gender, smoking status, histologic type or EGFR mutation status (Table 3)

Summary

Introduction

Aberrant microRNA expression has been implicated in metastasis of cancers. MiR-661 accelerates proliferation and invasion of breast cancer and ovarian cancer, while impedes that of glioma. MicroRNAs are 20–22 nt long non-protein-coding RNAs which involve in diverse physiological processes such as proliferation, apoptosis and differentiation [1]. They function as tumor suppressors or oncogenes by promoting degradation or inhibiting translation of regulatory factors through interactions at 3′ UTRs [2]. Another report yielded opposite results that miR-661 accelerates EMT and metastasis of breast cancer cells [10] Later research elucidated this seemly contradictory phenomenon with the view that miR-661 acts as tumor suppressor in cells with wild type p53 and oncogene in cells with mutated p53 [11].

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Conclusion