LncRNA NCK1-AS1 Aggravates Hepatocellular Carcinoma by the miR-22-3p/YARS Axis to Activate PI3K/AKT Signaling.

Abstract

BACKGROUND:

Hepatocellular carcinoma (HCC) is frequently diagnosed at late stages when curative treatments are no more appliable. Many studies have proved the active role of long non-coding RNAs (lncRNAs) in cancers' biology; here, the functional role of lncRNA NCK1-AS1 in HCC was identified.

METHODS:

Gene expression in tumor tissues of HCC was evaluated by examining online databases and 88 collected HCC samples from our hospital. The interactions of miR-22-3p with NCK1-AS1 and tyrosyl-tRNA synthetase (YARS) were tested by conducting bioinformatics analysis, luciferase report, and RNA pulldown experiments. CCK-8, colony formation, flow cytometry, wound healing, transwell experiments were used to dissect the role of the NCK1-AS1/miR-22-3p/YARS axis in HCC.

RESULTS:

NCK1-AS1 was overexpressed in HCC cells and tissues. Functional assays depicted that depletion of NCK1-AS1 hampered malignant character of HCC cells. NCK1-AS1 controlled the availability of miR-22-3p, resulting in YARS upregulation. YARS was found to have a clinical value for HCC diagnosis. Moreover, rescue experiments revealed that miR-22-3p inhibition or YARS overexpression partially blocked the function of NCK1-AS1 deficiency in HCC cells. As for the downstream signaling pathway, we discovered that NCK1-AS1 activated PI3K/AKT signaling by the miR-22-3p/YARS axis.

CONCLUSION:

The present study verified that NCK1-AS1 could promote HCC progression via the miR-22-3p/YARS axis to activate PI3K/AKT signaling.

• Authors: Weixin Zhou, Jie Wang, Jie Zhang, Yuhan Wang, Ling Jiang, Tianhong Guo, Binrui Luo, Qi Xu, Yuanshuai Huang
• Journal: Journal of gastrointestinal and liver diseases : JGLD (J Gastrointestin Liver Dis) Vol. 31 Issue 1 Pg. 48-59 (03 19 2022) ISSN: 1842-1121 [Electronic] Romania
• PMID: 35306563 (Publication Type: Journal Article)

Chemical References

• Adaptor Proteins, Signal Transducing
• MIRN22 microRNA, human
• MicroRNAs
• Nck protein
• Oncogene Proteins
• RNA, Long Noncoding
• Proto-Oncogene Proteins c-akt
• Tyrosine-tRNA Ligase

Topics

• Adaptor Proteins, Signal Transducing
• Carcinoma, Hepatocellular (pathology)
• Cell Line, Tumor
• Cell Proliferation (genetics)
• Gene Expression Regulation, Neoplastic
• Humans
• Liver Neoplasms (pathology)
• MicroRNAs (genetics, metabolism)
• Oncogene Proteins
• Phosphatidylinositol 3-Kinases (genetics, metabolism)
• Proto-Oncogene Proteins c-akt (genetics, metabolism)
• RNA, Long Noncoding (genetics)
• Signal Transduction
• Tyrosine-tRNA Ligase (genetics, metabolism)