Downregulation of miR-101 contributes to epithelial-mesenchymal transition in cisplatin resistance of NSCLC cells by targeting ROCK2.

Zhiqiang Ye,Songwang Cai,Zhongzhen Su,Ziqing Hei,Haibo Zhang,Mingjun Bai,Shengli Yin

doi:10.18632/oncotarget.6852

Zhiqiang Ye, Songwang Cai + Show 5 more

Open Access

https://doi.org/10.18632/oncotarget.6852

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Journal: Oncotarget	Publication Date: Jan 9, 2016
Citations: 48	License type: CC BY 2.5

Affiliation: Sun Yat-sen University

Abstract

Chemoresistance and epithelial-mesenchymal transition (EMT) in cancer are linked phenomena. EMT contributes to chemoresistance, however, little is known about whether chemotherapy can induce EMT in cancer cells. Here, we found that miR-101 expression was downregulated in cisplatin-resistant non-small cell lung cancer (NSCLC) cells. Restoration of miR-101 expression inhibited EMT and increased the sensitivity of cisplatin-resistant NSCLC cells to cisplatin in vitro by targeting ROCK2. Furthermore, ROCK2 protein level was inversely correlated with miR-101 level in NSCLC tissue samples. Kaplan-Meier analysis revealed that low miR-101 expression in NSCLC was correlated with poor survival time. In summary, our results provide novel mechanistic insights into the role of miR-101/ROCK2 signaling in the cisplatin resistance of NSCLC cells. Targeting of miR-101 is a potential therapeutic approach for NSCLC.

Highlights

Non-small-cell lung cancer (NSCLC) is the most common lung cancer and is the leading cause of death from cancer throughout the world [1]
We examined the levels of Rhoassociated coiled-coil containing protein kinase 2 (ROCK2) using western blotting and the results demonstrated that the levels of ROCK2 were upregulated in A549-res and NCIH520-res cells compared with their parental cells (Figure 3E), which were inversely correlated with the level of miR-101
We showed the functional role of low miR-101 expression in promoting epithelial-mesenchymal transition (EMT) in cisplatin-resistant non-small cell lung cancer (NSCLC) cells

Summary

Introduction

Non-small-cell lung cancer (NSCLC) is the most common lung cancer and is the leading cause of death from cancer throughout the world [1]. Tumor metastasis is the primary cause of death in NSCLC patients [2]. Surgical resection and adjuvant therapy can effectively treat NSCLC, patients with tumor metastasis are mostly incurable because of its systemic nature and the resistance of disseminated tumor cells to existing therapeutic agents, including chemotherapy [3]. Epithelial-mesenchymal transition (EMT) in cancer cells plays a critical role in tumor metastasis [5]. Accumulating evidence shows that EMT contributes chemoresistance, little is known about whether chemotherapy can induce EMT in cancer cells [6, 7]

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