Affiliation:
1. Affiliated Nantong Hospital 3 of Nantong University, Nantong, Jiangsu
2. Nantong University Affiliated Qidong Hospital, Nantong, Jiangsu
3. Affiliated Hospital of Nantong University, Nantong, Jiangsu
Abstract
Abstract
Growing evidence demonstrated long non coding RNAs (lncRNAs) are closely related with malignant progress in colorectal cancer (CRC), and seriously implicated in chemoresistance. 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. In this study, we aimed to investigate the effect of lncRNA-ABALON on proliferation, migration, apoptosis, sensitivity to 5-Fluorouracil (5-FU) and mitophagy in CRC cells. Indicated mRNAs and protein expressions were determined by quantitative real-time RT-PCR and western blot. CCK-8 was employed to evaluate IC50 of 5-FU and cell viability. Colony formation and flow cytometry were carried out for cell proliferation and apoptosis. We found ABALON expression was increased in CRC tissues, especially in CMS1 subtype and highly expressed ABALON was related with tumor differentiation, TNM staging, and lymph node metastasis (p < 0.05*). ABALON knockdown significantly led to impaired cell proliferation and enhanced apoptosis in CRC. Under different concentrations 5-FU stimulation, the IC50 of ABALON interference group were significantly declined than negative control group. ABALON overexpression promoted the IC50 of CRC cells to 5-FU. ABALON knocking down upregulated TOMM20 expression and suppressed LC3II, PTEN-induced putative kinase1 (PINK1), and E3 ubiquitin ligase (Parkin) expression. Furthermore, under 5-FU stimulation, inhibiting mitophagy reversed the increased colony formation, migration and cell apoptosis induced by ABALON overexpression. Collectively, our study proposed a novel perspective that ABALON potentiates cell proliferation, cell cycle, and apoptosis via PINK1/Parkin mediated mitophagy, and ABALON is a promising therapeutic target in reversing 5-FU resistance.
Publisher
Research Square Platform LLC