The long non‐coding RNA HCG18 promotes the growth and invasion of colorectal cancer cells through sponging miR‐1271 and upregulating MTDH/Wnt/β‐catenin

Abstract

Long non‐coding RNAs (lncRNAs) have recently emerged as key regulators of the occurrence and progression of various human cancers, including colorectal cancer. However, the regulatory mechanism of lncRNAs in the tumorigenesis of colorectal cancer remains poorly understood. In this study, we aimed to elucidate the potential role of lncRNA HCG18 in colorectal cancer. Herein, we found that HCG18 expression was significantly upregulated in colorectal cancer tissues and cell lines. Knockdown of HCG18 significantly inhibited the growth and invasion of colorectal cancer cells, while its overexpression had the opposite effect. Moreover, HCG18 was identified as a sponge of miR‐1271. Our results showed that knockdown of HCG18 markedly upregulated miR‐1271 expression in colorectal cancer cells. Notably, HCG18 expression was inversely correlated with miR‐1271 expression in colorectal cancer specimens. Further investigation revealed that HCG18 contributed to the enhancement of MTDH/Wnt/β‐catenin signalling in colorectal cancer cells. The antitumour effect of HCG18 inhibition was significantly reversed by miR‐1271 inhibition or MTDH overexpression. Overall, the results of our study demonstrate that HCG18 exerts a potential oncogenic function in colorectal cancer by enhancing MTDH/Wnt/β‐catenin signalling via sponging of miR‐1271, highlighting the importance of HCG18/miR‐1271/ MTDH/Wnt/β‐catenin signalling in the progression of colorectal cancer.

Identification of HCG18 and MCM3AP-AS1 That Associate With Bone Metastasis, Poor Prognosis and Increased Abundance of M2 Macrophage Infiltration in Prostate Cancer

“…Knockdown of HCG18 inhibited the proliferation, migration, invasion, metastasis, while induced the apoptosis of cancer cells. [31][32][33]36,37 Also, silencing of HCG18 suppressed the growth of xenografts in mice. 36 Mechanistically, HCG18 was reported to competitively bind to miR-140, 31 miR-214-3p, 32 miR-1271, 33 miR-34a-5p 35 and miR-152-3p 34 to respectively enhance the expressions of the target genes of these miRNAs, including cyclin D1, CENPM, MTDH, HMMR and DNAJB12.…”

Contributions of Gene Modules Regulated by Essential Noncoding RNA in Colon Adenocarcinoma Progression

“…XIST significantly increases its expression in both CRC tissue sample and CRC cells and promotes CRC cell proliferation by the miR-132-3p/MAPK1 axis [35]. HCG18 promotes the growth and invasion of CRC cell via miR-1271/MTDH/Wnt/βcatenin signaling [36]. High expression of HOXA11-AS is a risk factor for distant metastasis and poor clinical outcomes in numerous tumors [37].…”

Molecular Mechanisms of miR-1271 Dysregulation in Human Cancer

“…Wu et al (2017) suggested that BET-Bromodomain inhibitor JQ1 synergized ABT-263 against CRC cells by inhibiting c-Myc-induced miR-1271 expression. HCG18 exerts a potential oncogenic function in CRC by enhancing MTDH/Wnt/ b-catenin signaling through sponging of miR-1271 (Li et al, 2020). Xie et al (2018) showed in pancreatic cancer (PC) that miR-1271 negatively regulated AKT/mTOR signaling and promoted apoptosis by targeting PDK1 in PC.…”