Overexpression of MEG3 sensitizes colorectal cancer cells to oxaliplatin through regulation of miR-141/PDCD4 axis

Abstract

The existence of drug resistance is the main reason for chemotherapeutic failure in malignancies. Long non-coding RNA (lncRNA) maternally expressed gene 3 (MEG3) is implicated with tumorigenesis and chemoresistance. In the present study, we aimed to identify the role of MEG3 in oxaliplatin-resistant colorectal cancer (CRC) and its potential mechanisms. MEG3 was down-regulated in oxaliplatin-resistant CRC tissues and cell lines. Low MEG3 expression was correlated with poor prognosis of CRC patients. Overexpression of MEG3 improved oxaliplatin sensitivity of HT29/OXA and HCT116/OXA cells. MEG3 suppressed miR-141 expression in HCT116/OXA cells. Moreover, MEG3 elevated PDCD4 expression through targeting miR-141, acting as a competing endogenous RNA (ceRNA). miR-141 inhibition or PDCD4 up-regulation could mimic the functional role in oxaliplatin resistance, which was counteracted by overexpression of MEG3. Collectively, MEG3 facilitated the sensitivity of CRC cells to oxaliplatin by regulating miR-141/PDCD4 axis, providing a novel therapeutic strategy for CRC.