LncRNA ALKBH3-AS1 enhances ALKBH3 mRNA stability to promote hepatocellular carcinoma cell proliferation and invasion.

Abstract

Long noncoding RNAs (lncRNAs) are confirmed as the key regulators of hepatocellular carcinoma (HCC) occurrence and progression, but the role of AlkB homologue 3 antisense RNA 1 (ALKBH3-AS1) in HCC is unclear. We revealed the overexpression of ALKBH3-AS1 in HCC tissues. The upregulated levels of ALKBH3-AS1 were observed in HCC cells. ALKBH3-AS1 was expressed in the nucleus and cytoplasm of HCC cells. The high ALKBH3-AS1 expression was markedly associated with a decreased survival rate of HCC patients. ALKBH3-AS1 knockdown repressed and ALKBH3-AS1 overexpression enhanced HCC cell invasion and proliferation. ALKBH3-AS1 silencing restricted HCC growth in vivo. A significant positive correlation between ALKBH3-AS1 and ALKBH3 mRNA levels was confirmed in HCC specimens. ALKBH3-AS1 silencing reduced ALKBH3 expression by stabilizing its mRNA stability in HCC cells. Notably, the impact of ALKBH3 silencing on HCC cells was similar to that of ALKBH3-AS1 knockdown. ALKBH3 restoration prominently attenuated the suppressive effects resulting from ALKBH3-AS1 silencing in HCCLM3 cells. Hypoxia-inducible factor-1α (HIF-1α) transcriptionally activated ALKBH3-AS1 expression in hypoxic HCC cells. ALKBH3-AS1 knockdown markedly attenuated cell proliferation and invasion in hypoxic Huh7 cells. Collectively, HIF-1α-activated ALKBH3-AS1 exerted an oncogenic role by enhancing ALKBH3 mRNA stability in HCC cells.

• Authors: Qiliang Lu, Hao Wang, Xiangxiang Lei, Qiancheng Ma, Jie Zhao, Wen Sun, Cheng Guo, Dongsheng Huang, Qiuran Xu
• Journal: Journal of cellular and molecular medicine (J Cell Mol Med) Vol. 26 Issue 20 Pg. 5292-5302 (10 2022) ISSN: 1582-4934 [Electronic] England
• PMID: 36098205 (Publication Type: Journal Article)
• Copyright: © 2022 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.

Chemical References

• Hypoxia-Inducible Factor 1, alpha Subunit
• MicroRNAs
• RNA, Antisense
• RNA, Long Noncoding
• RNA, Messenger
• ALKBH3 protein, human
• AlkB Homolog 3, Alpha-Ketoglutarate-Dependent Dioxygenase

Topics

• AlkB Homolog 3, Alpha-Ketoglutarate-Dependent Dioxygenase (genetics, metabolism)
• Carcinoma, Hepatocellular (pathology)
• Cell Line, Tumor
• Cell Movement (genetics)
• Cell Proliferation (genetics)
• Gene Expression Regulation, Neoplastic
• Humans
• Hypoxia-Inducible Factor 1, alpha Subunit (metabolism)
• Liver Neoplasms (pathology)
• MicroRNAs (genetics)
• RNA Stability
• RNA, Antisense
• RNA, Long Noncoding (genetics, metabolism)
• RNA, Messenger (genetics)