Upregulation of microRNA-650 by PBX1 is correlated with the development of Helicobacter pylori-associated gastric carcinoma.

Abstract

Helicobacter pylori (HP) infection induces the development of gastric carcinoma (GC), one of the most frequent and fatal cancers worldwide, via a progressive cascade. The roles of microRNAs (miRNAs) involved in the cascade and the behind mechanisms, however, are still unclear. This study was designed to investigate the expression of miR-650, a well-recognized oncogenic miRNA in GC samples and to analyze the associations between this miRNA and HP infection, and the molecular mechanism. Following miRNA- and mRNA-based microarray analyses, miR-650, pre-B-cell leukemia transcription factor 1 (PBX1), and LATS2 were filtered as targets. After that, function assays were implemented to assess their function in GC cells. miR-650 was upregulated in HP+ tissues and cells, and inhibition of miR-650 attenuated cell proliferation, invasion, migration, yet enhanced apoptosis. PBX1 was overexpressed in HP+ tissues and cells and promoted miR-650 transcription. Overexpression of PBX1 abrogated the effect of the miR-650 inhibitor on GC cells. miR-650 targeted LATS2, and LATS2 was poorly expressed in HP+ tissues and cell lines. Simultaneous knockdown of miR-650 and LATS2 reduced GC cell apoptosis. These results display that upregulation of miR-650 induced by HP infection and PBX1 dampens LATS2 in GC cells, potentially offering novel intervention targets for GC.

• Authors: Junzheng Liu, Lei Wang, Jie Li, Yu Xu
• Journal: Neoplasma (Neoplasma) Vol. 68 Issue 2 Pg. 262-272 (Mar 2021) ISSN: 0028-2685 [Print] Slovakia
• PMID: 33147052 (Publication Type: Journal Article)

Chemical References

• MIRN650 microRNA, human
• MicroRNAs
• Pre-B-Cell Leukemia Transcription Factor 1
• Tumor Suppressor Proteins
• PBX1 protein, human
• LATS2 protein, human
• Protein Serine-Threonine Kinases

Topics

• Carcinoma
• Cell Line, Tumor
• Cell Movement
• Cell Proliferation
• Gene Expression Regulation, Neoplastic
• Helicobacter Infections (pathology)
• Helicobacter pylori
• Humans
• MicroRNAs (genetics)
• Pre-B-Cell Leukemia Transcription Factor 1 (genetics)
• Protein Serine-Threonine Kinases
• Stomach Neoplasms (genetics, microbiology)
• Tumor Suppressor Proteins
• Up-Regulation