regulates mitophagy and 5-FU sensitivity in colorectal cancer via PINK1-Parkin pathway.

Background: Growing evidence demonstrated that long non-coding RNAs (lncRNAs) are closely related with chemoresistance in colorectal cancer (CRC). Mitophagy serves as an essential factor to maintain the quality of tumor cells. However, it is unclear whether lncRNAs are involved in mitophagy regulation in CRC. The aim of this study is to evaluate whether lncRNAs are involved in regulating mitophagy and chemoresistance in CRC.

Methods: In this study, gain/loss of function was used to analyze the biological function influenced by apoptotic -antisense long non-coding RNA (). Western blot and JC-1 probe were carried out for detecting mitophagy. Chemosensitivity of CRC cells to 5-fluorouracil (5-FU) was determined using cell counting kit-8 (CCK-8), flow cytometry, colony formation and trans well assays.

Results: We found that expression was increased in CRC, especially in consensus molecular subtype 1 (CMS1) and highly expressed was related with tumor differentiation, tumor node metastasis (TNM) staging, and lymph node metastasis (P<0.05). knockdown led to impaired proliferation and enhanced apoptosis in CRC. Mitophagy variations primed by enhanced mitochondrial homeostasis. The half maximal inhibitory concentration (IC50) of 5-FU in interference groups declined, while overexpression elevated IC50. Furthermore, defective mitophagy not only rescued the proliferation, metastasis, and apoptosis induced by overexpression, but also, enhanced the anti-tumor effect of 5-FU .

Conclusions: Collectively, our study proposed that potentiates CRC progression via PINK1/Parkin mediated mitophagy, and is a promising therapeutic target in reversing 5-FU resistance.