Long non-coding RNA ADAMTS9-AS2 inhibits liver cancer cell proliferation, migration and invasion
Hanjun Li1,2, Hu Huang3,4, Sha Li5
1The First School of Clinical Medicine, Southern Medical University, Guangzhou, Guangdong 510515, P.R. China.
Abstract:
Long non-coding RNA (lncRNA) ADAM metallopeptidase with thrombospondin type 1 motif 9 antisense RNA 2 (ADAMTS9-AS2) is involved in various types of cancer, such as ovarian cancer, lung cancer and clear cell renal cell carcinoma. However, the roles of ADAMTS9-AS2 in liver cancer are not completely understood. The present study aimed to determine the functional role of ADAMTS9-AS2 in human liver cancer and investigate the potential underlying molecular mechanisms. The expression levels of ADAMTS9-AS2 and ADAMTS9 were determined following ADAMTS9-AS2 overexpression and knockdown. The results indicated that ADAMTS9-AS2 overexpression and knockdown increased and decreased ADAMTS9 mRNA and protein expression levels, respectively, indicating that alterations in ADAMTS9 expression corresponded with ADAMTS9-AS2 expression. Subsequently, the effects of ADAMTS9-AS2 on liver cancer cell proliferation, migration and invasion were analyzed by performing Cell Counting Kit-8, wound healing and Transwell assays, respectively. The results demonstrated that ADAMTS9-AS2 inhibited liver cancer cell proliferation, migration and invasion. Finally, the effect of ADAMTS9 on PI3K/AKT/mTOR signaling pathway-associated proteins [AKT, phosphorylated-AKT, phosphatidylinositol-4, 5-bisphosphate 3-kinase catalytic subunit β (PIK3CB), mTOR and phosphorylated-mTOR], several key autophagy-related proteins [light chain 3-I/II (LC3-I/II), beclin 1 (BECN1) and sequestosome 1 (SQSTM1)] and apoptosis-related proteins (Bax and Bcl-2) was detected via western blotting. The results suggested that ADAMTS9-AS2 downregulated the phosphorylation of AKT and mTOR, the protein expression level of PIK3CB, as well as the expression levels of autophagy protein SQSTM1 and antiapoptotic protein Bcl-2. By contrast, ADAMTS9-AS2 upregulated the expression levels of autophagy proteins LC3-II and BECN1, and the proapoptotic protein Bax. Collectively, ADAMTS9-AS2 inhibited liver cancer cell proliferation, migration and invasion via inhibiting the PI3K/AKT/mTOR signaling pathway. The present study provided a novel insight into the role of ADAMTS9-AS2 in liver cancer.
Insights
Long non-coding RNA ADAMTS9-AS2 inhibits liver cancer progression by downregulating the PI3K/AKT/mTOR pathway. This study reveals ADAMTS9-AS2 as a potential therapeutic target for liver cancer, impacting cell proliferation, migration, and invasion.
Area of Science:
- Molecular Biology
- Oncology
- Genetics
Background:
- Long non-coding RNA (lncRNA) ADAM metallopeptidase with thrombospondin type 1 motif 9 antisense RNA 2 (ADAMTS9-AS2) is implicated in various cancers.
- The specific role of ADAMTS9-AS2 in human liver cancer remains largely unelucidated.
Purpose of the Study:
- To investigate the functional role of ADAMTS9-AS2 in human liver cancer.
- To explore the underlying molecular mechanisms by which ADAMTS9-AS2 influences liver cancer progression.
Main Methods:
- Assessed ADAMTS9-AS2 and ADAMTS9 expression levels following overexpression and knockdown.
- Utilized Cell Counting Kit-8, wound healing, and Transwell assays to evaluate cell proliferation, migration, and invasion.
- Analyzed protein expression of key signaling molecules (PI3K/AKT/mTOR pathway), autophagy markers (LC3-I/II, BECN1, SQSTM1), and apoptosis regulators (Bax, Bcl-2) via Western blotting.
Main Results:
- ADAMTS9-AS2 expression positively correlated with ADAMTS9 mRNA and protein levels.
- ADAMTS9-AS2 significantly inhibited liver cancer cell proliferation, migration, and invasion.
- ADAMTS9-AS2 downregulated PI3K/AKT/mTOR signaling, reduced SQSTM1 and Bcl-2, and increased LC3-II, BECN1, and Bax expression.
Conclusions:
- ADAMTS9-AS2 functions as a tumor suppressor in liver cancer.
- The inhibitory effects of ADAMTS9-AS2 are mediated through the suppression of the PI3K/AKT/mTOR signaling pathway.
- ADAMTS9-AS2 represents a potential therapeutic target for liver cancer treatment.
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