Oncogenic miR-19a and miR-19b co-regulate tumor suppressor MTUS1 to promote cell proliferation and migration in lung cancer

Yuanyuan Gu,Tao Wang,Chen Wang,Junfeng Zhang,Mengchao Yu,Zhicong Liao,Yong Zhou,Xi Chen,Shuoxin Liu,Guimin Chen,Xiaodan Zhang,Hongwei Liang,Chen-Yu Zhang

doi:10.1007/s13238-017-0393-7

Abstract

ABSTRACTMTUS1 (microtubule-associated tumor suppressor 1) has been identified that can function as a tumor suppressor gene in many malignant tumors. However, the function and mechanisms underlying the regulation of MTUS1 are unclear. In the present study, we reported that miR-19a and miR-19b (miR-19a/b) promote proliferation and migration of lung cancer cells by targeting MTUS1. First, MTUS1 was proved to function as a tumor suppressor in lung cancer and was linked to cell proliferation and migration promotion. Second, an inverse correlation between miR-19a/b expression and MTUS1 mRNA/protein expression was noted in human lung cancer tissues. Third, MTUS1 was appraised as a direct target of miR-19a/b by bioinformatics analysis. Fourth, direct MTUS1 regulation by miR-19a/b in lung cancer cells was experimentally affirmed by cell transfection assay and luciferase reporter assay. Finally, miR-19a/b were shown to cooperatively repress MTUS1 expression and synergistically regulate MTUS1 expression to promote lung cancer cell proliferation and migration. In conclusion, our findings have provided the first clues regarding the roles of miR-19a/b, which appear to function as oncomirs in lung cancer by downregulating MTUS1.

Highlights

All over the world, lung cancer has been the leading cause of cancer-related death (Ramalingam et al, 1998)
After measuring the levels of microtubule-associated tumor suppressor 1 (MTUS1) protein expression in 9 pairs of lung cancer tissue samples and corresponding normal adjacent tissue samples, we found that MTUS1 protein levels were significantly lower in lung cancer tissues than in normal tissues (Fig. 1A and 1B)
We evaluated the biological functions of MTUS1 in lung cancer cell line A549

Summary

Introduction

Lung cancer has been the leading cause of cancer-related death (Ramalingam et al, 1998). The 56% of lung cancers are diagnosed during the late stages of disease while the early stages of disease are usually asymptomatic; only 15% of cases can be diagnosed during a local stage (Siegel et al, 2012). Many carcinogenic factors, such as smoking, genetic mutations and declining immune function, may increase the risk of developing lung cancer. The exact mechanisms underlying the development of lung cancer remain complex and poorly understood. These obstacles underscore the need for indepth exploration for genes that are aberrantly expressed during lung carcinogenesis, and the need for intensive investigations of the roles of these genes in tumor biology

Methods

Results

Conclusion