LINC01018 confers a novel tumor suppressor role in hepatocellular carcinoma through sponging microRNA-182-5p

Abstract

Hepatocellular carcinoma (HCC) is the second leading cause of cancer-related mortality. Emerging evidence has demonstrated that some long noncoding RNAs (lncRNAs) are involved in the development and progression of HCC. Herein, the current study aimed to explore the potential mechanism of LINC01018 in regulating the progression of HCC. Initially, the expression of LINC01018, microRNA-182-5p (miR-182-5p), and forkhead box protein O1 (FOXO1) was quantified in 72 paired HCC and adjacent normal tissue samples as well as HCC cells, followed by identification of the interaction among them. To define the contributory role of LINC01018 in the progression of HCC, the expression of LINC01018, miR-182-5p, or FOXO1 was altered in HCC cells, followed by evaluation of cell proliferation, cell cycle distribution, and cell apoptosis. Finally, in vivo tests were performed to further verify the role of LINC01018 in HCC. It was observed that LINC01018 and FOXO1 were poorly expressed but miR-182-5p was highly expressed in HCC tissues and cells. The upregulation of LINC01018 was shown to decrease proliferation while promoting apoptosis of HCC cells. LINC01018 acted as a sponge of miR-182-5p, which targeted FOXO1. Last, mice injected with Hep3B overexpressing FOXO1 displayed suppressed xenograft tumor formation. Collectively, overexpression of LINC01018 represses proliferation and promotes apoptosis of HCC cells via upregulation of FOXO1 by sponging miR-182-5p, which highlights overexpression of LINC01018 as a candidate suppressor of HCC. NEW & NOTEWORTHY This study provides evidence for understanding the molecular mechanism involved in the progression of hepatocellular carcinoma and identifies a novel network of LINC01018/miR-182-5p/FOXO1. We also conducted in vivo experiments in nude mice to validate the anti-tumor effect of LINC01018.

Pan-cancer characterization of expression and clinical relevance of m6A-related tissue-elevated long non-coding RNAs

“…F11-AS1 can inhibit HBV-related hepatocellular carcinoma progression by regulating NR1I3 via binding to microRNA-211-5p. LINC01018 has a novel tumor suppressor role in hepatocellular carcinoma by sponging miR-182-5p [9,10]. We also found lower expression of m 6 A-modified MIR325HG to be correlated with worse patient survival in both LGG and GBM (Fig.…”

Identification of Novel lncRNAs in Ovarian Cancer and Their Impact on Overall Survival

“…LINC01363, which is related to worse prognosis, has been shown to be upregulated in breast, ovarian, and cervical cancer [ 19 ]. However, most interestingly, LINC01018, which was associated with a worse response to initial chemotherapy in our model, has been linked to progression in hepatocellular carcinoma (HCC) [ 20 ]. LINC01018 is downregulated in HCC, thereby decreasing the expression of FOXO1, which prevents apoptosis.…”

New LncRNAs in Chronic Hepatitis C progression: from fibrosis to hepatocellular carcinoma

“…LINC01018, also called SRHC, was down-regulated in HCC, corroborating the findings of Zheng et al 53 that found lower levels of expression in HCC samples with a high serum a-fetoprotein level and a low degree of differentiated tumors. In addition, up-regulation of LINC01018 was shown to decrease proliferation while promoting apoptosis of HCC cells 54 . LINC02027 (alias LOC728290) was found down-regulated in HCC, as also observed by Zhang et al 55 .…”