MYC-activated lncRNA HNF1A-AS1 overexpression facilitates glioma progression via cooperating with miR-32-5p/SOX4 axis.

Abstract

Mounting literatures have revealed the crucial effects of long noncoding RNA (lncRNA) in various cancers, including glioma. HNF1A-AS1, a novel lncRNA, is reported to modulate tumorigenesis and development of multiple cancers. However, the tumorigenic function of lncRNA HNF1A-AS1 in glioma remains largely unknown. quantitative reverse transcription and polymerase chain reaction and western blot assays were applied to evaluate the expression of relevant mRNAs and proteins. 5-Ethynyl-2'- deoxyuridine, terminal deoxynucleotidyl transferase dUTP nick-end labeling, flow cytometry, and transwell assays were conducted for examining the influence of HNF1A-AS1 on glioma cell functions. The relationship among RNAs was investigated by mechanical experiments. The results demonstrated that HNF1A-AS1 was predominantly highly expressed in glioma cell lines compared with nontumor glial epithelial cell, which was associated with the stimulation of transcription factor myelocytomatosis oncogene. Knockdown of HNF1A-AS1 remarkably inhibited glioma cells proliferation, migration, and invasion, while accelerating cell apoptosis in vitro. Mechanically, HNF1A-AS1 served as a miR-32-5p sponge. Moreover, SOX4 was discovered as a target of miR-32-5p. Inhibited miR-32-5p or upregulated SOX4 could markedly counteract the inhibitory effects of silencing HNF1A-AS1 on glioma malignant biological behaviors. HNF1A-AS1 exerted oncogenic property in glioma progression via upregulating miR-32-5p-mediated SOX4 expression, suggesting potential novel therapeutic target for future glioma treatment.

• Authors: Jianheng Wu, Rong Li, Linfan Li, Yimian Gu, Hui Zhan, Changbao Zhou, Chuanhong Zhong
• Journal: Cancer medicine (Cancer Med) Vol. 9 Issue 17 Pg. 6387-6398 (09 2020) ISSN: 2045-7634 [Electronic] United States
• PMID: 33448691 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2020 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

Chemical References

• MIRN32 microRNA, human
• MYC protein, human
• MicroRNAs
• Neoplasm Proteins
• Proto-Oncogene Proteins c-myc
• RNA, Long Noncoding
• SOX4 protein, human
• SOXC Transcription Factors
• Transcription Factors
• long non-coding RNA HNF1A-AS1, human
• DNA Nucleotidylexotransferase
• 5-ethynyl-2'-deoxyuridine
• Deoxyuridine

Topics

• Animals
• Apoptosis
• Brain Neoplasms (etiology, metabolism, pathology)
• Cell Line, Tumor
• DNA Nucleotidylexotransferase
• Deoxyuridine (analogs & derivatives)
• Disease Progression
• Flow Cytometry
• Gene Silencing
• Glioma (etiology, metabolism, pathology)
• Humans
• In Situ Nick-End Labeling
• Male
• Mice
• Mice, Nude
• MicroRNAs (metabolism)
• Neoplasm Proteins (metabolism)
• Proto-Oncogene Proteins c-myc (metabolism)
• RNA, Long Noncoding (genetics, metabolism)
• SOXC Transcription Factors (metabolism)
• Transcription Factors (metabolism)