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.

vtRNA2-1/nc886 Produces a Small RNA That Contributes to Its Tumor Suppression Action through the microRNA Pathway in Prostate Cancer

“…Indeed, snc886-3p enrichment is above the average of the microRNAs in these experiments, indicating a specialized microRNA-like function for this small RNA product in comparison to the 5p. Although our study shows a low association of snc886-5p to AGO it does not rule out the function of snc886-5p as a microRNA, which has been shown previously in other tissues (brain [19], cervical [66,67], breast [68]). Alternatively, snc886-5p might be involved in another pathway or be a non-functional secondary product of nc886 processing.…”

Heritable methylation marks associated with breast and prostate cancer risk

“…Work by us and by others also shows that a high proportion (73-80%) of nontumor tissues have monoallelic methylation at VTRNA2-1. 14,29,30 The VTRNA2-1 RNA molecule can act as a tumor suppressor by downregulating the RNA-activated protein kinase R. 31 A disruption to the VTRNA2-1 allele-specific methylation is common in cancer tissues 29 and promoter methylation has been associated with cervical cancer, 32 lung cancer, 33 and acute myeloid leukemia. 30 A recent study that included data from the MCCS reported associations of the VTRNA2-1…”

Preeclampsia: novel insights from global RNA profiling of trophoblast subpopulations

“…Thus, the eCTB subpopulation might play a role in the dysregulation of the renin-angiotensin system that is observed in preeclampsia. 73 This category of differential expression genes also included CHI3L1 (a glycosidase that is an important modulator of the tumor microenvironment), 74 VTRNA2-1 (which plays important roles in apoptosis), 75 HMOX1, and KDR (VEGFR-2), which we previously showed was down-regulated as cytotrophoblasts differentiate along the invasive pathway. 30 Its up-regulation in the context of sPE is consistent with deficits in eCTB differentiation.…”