Oncotarget

Research Papers:

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

Lu Kong, Qi Hao, Ying Wang, Ping Zhou, Binbin Zou and Yu-xiang Zhang _

PDF  |  HTML  |  Supplementary Files  |  How to cite  |  Order a Reprint

Oncotarget. 2015; 6:28371-28388. https://doi.org/10.18632/oncotarget.4948

Metrics: PDF 934 views  |   HTML 1162 views  |   ?  


Abstract

Lu Kong1, Qi Hao1, Ying Wang1, Ping Zhou2, Binbin Zou1 and Yu-xiang Zhang1,3,4

1 Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Capital Medical University, Beijing, China

2 Department of Bioinformatics and Computer Science, School of Biomedical Engineering, Capital Medical University, Beijing, China

3 Cancer Institute of Capital Medical University, Beijing, China

4 Beijing Key Laboratory for Cancer Invasion and Metastasis Research, Capital Medical University, Beijing, China

Correspondence to:

Yu-xiang Zhang, email:

Keywords: non-coding microRNAs, p53, cervical cancer, VTRNA2-1-5p, apoptosis

Received: December 17, 2014 Accepted: July 02, 2015 Published: July 22, 2015

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.


Creative Commons License All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 3.0 License.
PII: 4948