Regulation of p53 expression and apoptosis by vault RNA2-1-5p in cervical cancer cells.

Abstract

nc886 or VRNA2-1 has recently been identified as a noncoding RNA instead of a vault RNA or a pre-microRNA. Several studies have reported that pre-miR-886 plays a tumor-suppressive role in a wide range of cancer cells through its activity as a cellular protein kinase RNA-activated (PKR) ligand and repressor. However, by sequencing stem-PCR products, we found that a microRNA originating from this precursor, vault RNA2-1-5p (VTRNA2-1-5p), occurs in cervical cancer cells. The expression levels of the predicted targets of VTRNA2-1-5p are negatively correlated with VTRNA2-1-5p levels by quantitative reversion transcription PCR (qRT-PCR). Previous results have shown that VTRNA2-1-5p is overexpressed in human cervical squamous cell carcinomas (CSCCs) compared with adjacent healthy tissues. Inhibition of VTRNA2-1-5p increases Bax protein expression and apoptotic cell death in cervical cancer cells. Our findings suggest that VTRNA2-1-5p has oncogenic activity related to the progression of cervical cancer. Here, we report that VTRNA2-1-5p directly targeted p53 expression and functioned as an oncomir in cervical cancer. VTRNA2-1-5p inhibition decreased cervical cancer cell invasion, proliferation, and tumorigenicity while increasing apoptosis and p53 expression. Interestingly, VTRNA2-1-5p inhibition also increased cisplatin-induced apoptosis of HeLa and SiHa cells. In human clinical cervical cancer specimens, low p53 expression and high VTRNA2-1-5p expression were positively associated.In addition, VTRNA2-1-5p was found to directly target the 5' and 3' untranslated regions (UTRs) of p53. We propose that VTRNA2-1-5p is a direct regulator of p53 and suggest that it plays an essential role in the apoptosis and proliferation of cervical cancer cells.

• Authors: Lu Kong, Qi Hao, Ying Wang, Ping Zhou, Binbin Zou, Yu-xiang Zhang
• Journal: Oncotarget (Oncotarget) Vol. 6 Issue 29 Pg. 28371-88 (Sep 29 2015) ISSN: 1949-2553 [Electronic] United States
• PMID: 26318295 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• 3' Untranslated Regions
• Antineoplastic Agents
• MIRN886 microRNA, human
• MicroRNAs
• Tumor Suppressor Protein p53
• Cisplatin

Topics

• 3' Untranslated Regions (genetics)
• Animals
• Antineoplastic Agents (pharmacology)
• Apoptosis (drug effects, genetics)
• Base Sequence
• Blotting, Western
• Carcinoma, Squamous Cell (genetics, metabolism, pathology)
• Cell Line, Tumor
• Cell Proliferation (drug effects, genetics)
• Cisplatin (pharmacology)
• Female
• Gene Expression Regulation, Neoplastic
• HeLa Cells
• Humans
• Immunohistochemistry
• In Situ Hybridization
• Mice, Inbred BALB C
• Mice, Nude
• MicroRNAs (genetics)
• Molecular Sequence Data
• Reverse Transcriptase Polymerase Chain Reaction
• Transplantation, Heterologous
• Tumor Suppressor Protein p53 (genetics, metabolism)
• Uterine Cervical Neoplasms (genetics, metabolism, pathology)