LncRNA SNHG6 promotes chemoresistance through ULK1-induced autophagy by sponging miR-26a-5p in colorectal cancer cells

被引：91

作者：

Wang, Xinke ^{[1
]}

Lan, Zhixian ^{[1
]}

He, Juan ^{[1
]}

Lai, Qiuhua ^{[1
]}

Yao, Xiang ^{[1
]}

Li, Qingyuan ^{[1
]}

Liu, Yongfeng ^{[1
]}

Lai, Huasheng ^{[1
]}

Gu, Chuncai ^{[1
]}

Yan, Qun ^{[1
]}

Fang, Yuxin ^{[1
]}

Zhang, Yue ^{[1
]}

Li, Aimin ^{[1
]}

Liu, Side ^{[1
]}

机构：

[1] Southern Med Univ, Guangdong Prov Key Lab Gastroenterol, Dept Gastroenterol, Nanfang Hosp, 1838 Guangzhou Ave North, Guangzhou, Guangdong, Peoples R China

来源：

CANCER CELL INTERNATIONAL | 2019年 / 19卷 / 01期

基金：

中国博士后科学基金;

关键词：

Colorectal cancer; SNHG6; ULK1-induced autophagy; Chemoresistance; ceRNA; COMPETING ENDOGENOUS RNA; LONG NONCODING RNA; SIGNALING PATHWAY; EXPRESSION; PROLIFERATION; PROGRESSION; MECHANISMS; UPF1; EMT;

D O I：

10.1186/s12935-019-0951-6

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Background Chemotherapy resistance is one of the main causes of recurrence in colorectal cancer (CRC) patients and leads to poor prognosis. Long noncoding RNAs (lncRNAs) have been reported to regulate chemoresistance. We aimed to determine the role of the lncRNA small nucleolar RNA host gene 6 (SNHG6) in CRC cell chemoresistance. Methods Cell drug sensitivity tests and flow cytometry were performed to analyze CRC cell chemoresistance. Animal models were used to determine chemoresistance in vivo, and micro RNA (miRNA) binding sites were detected by dual-luciferase reporter assays. Bioinformatics analysis was performed to predict miRNAs binding to SNHG6 and target genes of miR-26a-5p. SNHG6/miR-26a-5p/ULK1 axis and autophagy-related proteins were detected by qRT-PCR and western blotting. Furthermore, immunofluorescence was employed to confirm the presence of autophagosomes. Results SNHG6 enhanced CRC cell resistance to 5-fluorouracil (5-FU), promoted autophagy, inhibited 5-FU-induced apoptosis, and increased 5-FU resistance in vivo. Bioinformatics analysis showed that miR-26a-5p might bind to SNHG6 and target ULK1, and dual-luciferase reporter assays confirmed this activity. qRT-PCR and western blotting showed that SNHG6 was able to negatively regulate miR-26a-5p but correlated positively with ULK1. Conclusion SNHG6 may promote chemoresistance through ULK1-induced autophagy by sponging miR-26a-5p in CRC cells.

引用

页数：12