Long non‐coding RNA LINC00467 drives hepatocellular carcinoma progression via inhibiting NR4A3

Abstract

Hepatocellular carcinoma (HCC) is a main cause of cancer‐related deaths globally. Long non‐coding RNAs (lncRNAs) play important roles in diverse cancers. Our previous microarray‐based lncRNA profiling showed that LINC00467 was highly expressed in HCC. Here, we further explored the expression, role and functional mechanism of lncRNA LINC00467 in HCC. Our findings revealed that LINC00467 was up‐regulated in HCC tissues and HCC cell lines. Increased expression of LINC00467 was positively associated with tumour size and vascular invasion. In vitro functional experiments revealed that LINC00467 accelerated HCC cell proliferation, cell cycle progression and migration and reduced HCC cell apoptosis. In vivo functional assays revealed that LINC00467 drove HCC xenograft growth and HCC cell proliferation and repressed HCC cell apoptosis in vivo. Moreover, LINC00467 inhibited NR4A3 post‐transcriptionally via interacting with NR4A3 mRNA to form double‐stranded RNA, which was further degraded by Dicer. The expression of NR4A3 was inversely associated with LINC00467 in HCC tissues. Functional rescue assays found that restore of NR4A3 expression blocked the oncogenic roles of LINC00467 in HCC. Taken together, our results demonstrated that lncRNA LINC00467 was a novel highly expressed and oncogenic lncRNA in HCC via inhibiting NR4A3. Targeting LINC00467 or enhancing NR4A3 may be potential therapeutic strategies against HCC.

Bioinformatic analysis and validation of microRNA‐508‐3p as a protective predictor by targeting NR4A3/MEK axis in pulmonary arterial hypertension

“…NR4A3 embraces different characterize of biological functions upon specific pathogenesis of diseases. [33][34][35][36][37] Based on the two mRNA datasets, NR4A3 is up-regulated in PAH samples, consistent with our findings. In vivo experiment, we found that NR4A3 was up-regulated in MCT-PAH rat model tissues and in vitro experiment.…”

Long Noncoding RNA LINC00467: Role in Various Human Cancers

“…It is worth noting that studies on HCC have shown that LINC00467 expression is higher in HCC tissues than in controls ( Jiang et al, 2020 ; Wang et al, 2020 ; Zheng et al, 2020 ) However, Cai et al (2019 ) reported the opposite result in their clinical samples. Furthermore, they found that LINC00467 expression in HCC tissues with metastasis was lower than that in non-metastatic tissues.…”

“…( Jiang et al, 2020 ) In addition, LINC00467 can post-transcriptionally reduce the expression of the tumor suppressor NR4A3 by regulating Dicer-dependent RNA splicing, which ultimately contributes to HCC tumorigenesis. ( Wang et al, 2020 )…”

LncRNA LINC00467 acted as an oncogene in esophageal squamous cell carcinoma by accelerating cell proliferation and preventing cell apoptosis via the miR‐485‐5p/DPAGT1 axis

“…The aberrant expression of LINC00467 has been identified in diverse tumors like hepatocellular carcinoma, glioma, and neuroblastoma 16,34,35 . Especially, upregulated LINC00467 exhibited oncogenic roles to promote cell proliferation or prevented cell apoptosis in lung adenocarcinoma 36 .…”