Long noncoding RNA HOTAIRM1 inhibits cell progression by regulating miR-17-5p/ PTEN axis in gastric cancer.

Abstract

OBJECTIVES:

This study was conducted to identify the significantly altered long noncoding RNAs (lncRNAs), messenger RNA (mRNA) and pathways in gastric cancer (GC).

METHODS:

We used microarray analysis to identify differentially expressed lncRNAs and mRNAs, whereas the obviously changed pathways were found by gene set enrichment analysis. The coexpression network of lncRNA and mRNA was constructed by Cytoscape, and their target relationships with miRNAs were predicted by miRcode and TargetScan. qRT-PCR and Western blot were performed to determine the expression levels of mRNAs and proteins in tissues and cell lines. Dual-luciferase reporter assay was applied to achieve the determination of the specific target relationships. Cell viability, migration, and apoptosis were detected by MTT assay, wound healing assay and flow cytometry, respectively. Through the xenograft assay, the gastric tumor was implanted into nude mice to investigate the influence of HOTAIRM1 in vivo.

RESULTS:

HOTAIRM1 and phosphatase and tensin homolog (PTEN) were both downregulated in GC, whereas miR-17-5p was upregulated. Moreover, the PI3K/AKT pathway was found activated in GC. HOTAIRM1 targeted miR-17-5p, whereas PTEN was the downstream target gene of miR-17-5p. HOTAIRM1 suppressed proliferation and migration of GC cell line and induced their apoptosis, whereas miR-17-5p played the opposite role on GC cell line. HOTAIRM1 also postponed tumor growth in vivo and inhibited the PI3K/AKT pathway in GC.

CONCLUSIONS:

LncRNA HORAIRM1 suppressed the PI3K/AKT pathway in GC and inhibited the progression of GC by serving as a competing endogenous RNA of miR-17-5p, mediating the expression of PTEN.

• Authors: Ruiqi Lu, Gang Zhao, Yulong Yang, Zhaoyan Jiang, Jingli Cai, Zhijue Zhang, Hai Hu
• Journal: Journal of cellular biochemistry (J Cell Biochem) Vol. 120 Issue 4 Pg. 4952-4965 (04 2019) ISSN: 1097-4644 [Electronic] United States
• PMID: 30302796 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2018 Wiley Periodicals, Inc.

Chemical References

• MIRN17 microRNA, human
• MicroRNAs
• RNA, Neoplasm
• long non-coding RNA HOTAIRM1, human
• PTEN Phosphohydrolase
• PTEN protein, human

Topics

• Cell Line, Tumor
• Gene Expression Regulation, Neoplastic
• Humans
• MicroRNAs (genetics, metabolism)
• PTEN Phosphohydrolase (genetics, metabolism)
• RNA, Neoplasm (genetics, metabolism)
• Signal Transduction
• Stomach Neoplasms (genetics, metabolism, pathology)