MiR-194 inhibits the proliferation, invasion, migration, and enhances the chemosensitivity of non-small cell lung cancer cells by targeting forkhead box A1 protein.

Xuchao Zhu,Fei Yu,Dan Li,Jing Xie,Zhongwei Lv,Lihong Fan,Qiong Luo,Suyun Fan,Yushui Ma,Haidong Cai,Chengyou Jia

doi:10.18632/oncotarget.7545

Abstract

Recent studies have implied that miRNAs may play a crucial role in tumor progression and may be involved in the modulation of some drug resistance in cancer cells. Earlier studies have demonstrated that miR-194 was involved in tumor metastasis and drug resistance in non-small cell lung cancer (NSCLC), whereas their expression and roles on NSCLC still need further elucidation. In the current study, we found that miR-194 is decreased in NSCLC samples compared with adjacent non-cancerous lung samples, and low expression of miR-194 predicts poor patient survival. Both in vitro and in vivo experiments showed that ectopic stable expression miR-194 suppressed proliferation, migration, invasion and metastasis and induced apoptosis in NSCLC cells and that this suppression could be reversed by reintroducing forkhead box A1 (FOXA1), a functional target of miR-194. In addition, miR-194 was downregulated in in cisplatin-resisted human NSCLC cell line-A549/DDP and overexpression of miR-194 increases cisplatin sensitivity. These findings suggested that miR-194 inhibits proliferation and metastasis and reverses cisplatin-resistance of NSCLC cells and may be useful as a new potential therapeutic target for NSCLC.

Highlights

Non-small cell lung cancer (NSCLC) is one of the most common cancers and one of the leading causes of cancer related mortality across the world [1]
MiR-194 may play an indirect role in the prevention of hepatocellular carcinoma (HCC), it has been shown to regulate the hepatitis C virus binding target CD81, thereby preventing entry of the virus into hepatocytes [33]
We have demonstrated a mechanism that miR-194 was decreased in clinical NSCLC tissues compared to adjacent normal lung tissues and that miR194 played a critical role in NSCLC progression by regulating cell proliferation and invasion via negatively regulate forkhead box A1 (FOXA1)

Summary

Introduction

Non-small cell lung cancer (NSCLC) is one of the most common cancers and one of the leading causes of cancer related mortality across the world [1]. Most common pulmonary malignancy are NSCLC, it accounts for 85% of cases of pulmonary malignancies [2]. The most effective treatment for NSCLC is surgical resection, but most of patients diagnosed with NSCLC have reached an advanced pathological stage, at which point the patients miss the best time for surgical resection. Despite significant advances in surgery, chemotherapy and radiotherapy, the 5-year survival rate for lung cancer was only 15%. New treatment strategies to identify new molecular targets for prevention and treatment of NSCLC are urgently needed. MicroRNAs (miRNAs) are a class of single-stranded noncoding RNA molecules of 18–24 nucleotides in length

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Conclusion