Open AccessLncRNA ALKBH3‐AS1 enhances ALKBH3 mRNA stability to promote hepatocellular carcinoma cell proliferation and invasion
Author(s) -
Lu Qiliang,
Wang Hao,
Lei Xiangxiang,
Ma Qiancheng,
Zhao Jie,
Sun Wen,
Guo Cheng,
Huang Dongsheng,
Xu Qiuran
Publication year - 2022
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.17558
Subject(s) - gene knockdown , gene silencing , antisense rna , cancer research , cell growth , biology , long non coding rna , cell culture , rna interference , messenger rna , downregulation and upregulation , cell , small interfering rna , microbiology and biotechnology , transfection , rna , gene , biochemistry , genetics
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.