miR-134-5p Promotes Stage I Lung Adenocarcinoma Metastasis and Chemoresistance by Targeting DAB2

Liang Zhang; Ping Huang; Qing Li; Dong Wang; Cheng-Xiong Xu

doi:10.1016/j.omtn.2019.09.025

miR-134-5p Promotes Stage I Lung Adenocarcinoma Metastasis and Chemoresistance by Targeting DAB2

Mol Ther Nucleic Acids. 2019 Dec 6:18:627-637. doi: 10.1016/j.omtn.2019.09.025. Epub 2019 Oct 3.

Authors

Liang Zhang¹, Ping Huang¹, Qing Li¹, Dong Wang², Cheng-Xiong Xu³

Affiliations

¹ Cancer Center, Daping Hospital and Research Institute of Surgery, Third Military Medical University, Chongqing 400042, China.
² Cancer Center, Daping Hospital and Research Institute of Surgery, Third Military Medical University, Chongqing 400042, China. Electronic address: dongwang64@hotmail.com.
³ Cancer Center, Daping Hospital and Research Institute of Surgery, Third Military Medical University, Chongqing 400042, China. Electronic address: xuchengxiong@tmmu.edu.cn.

Abstract

Despite surgery and adjuvant therapy, early-stage lung adenocarcinoma (LUAD) treatment often fails due to local or metastatic recurrence. However, the mechanism is largely unknown. Here, we report that increased expression levels of miR-134-5p and decreased levels of disabled-2 (DAB2) were significantly correlated with recurrence in stage I LUAD patients. Our data show that miR-134-5p overexpression or DAB2 silencing strongly stimulated LUAD cell metastasis and chemoresistance. In contrast, inhibition of miR-134-5p or overexpression of DAB2 strongly suppressed LUAD cell metastasis and overcame the insensitivity of chemoresistant LUAD cells to chemotherapy. In addition, we demonstrated that DAB2 is a target of miR-134-5p and that miR-134-5p stimulates chemoresistance and metastasis through DAB2 in LUAD. Taken together, these findings suggest that miR-134-5p and its target gene DAB2 have potential as a biomarker for predicting recurrence in stage I LUAD patients. Additionally, miR-134-5p inhibition or DAB2 restoration may be a novel strategy for inhibiting LUAD metastasis and overcoming LUAD cell resistance to chemotherapy.

Keywords: DAB2; chemoresistance; metastasis; miR-134-5p; recurrence; stage I LUAD.