Downregulation of miR-221/222 by a microRNA sponge promotes apoptosis in oral squamous cell carcinoma cells through upregulation of PTEN

Abstract

MicroRNA-221 and microRNA-222 (miR-221/222) have been identified as oncogenes and confirmed to be overexpressed in various types of cancer. However, the regulation mechanism of miR-221/222 in oral squamous cell carcinoma (OSCC) remains to be fully elucidated. Previously, an miR-221/222 sponge was successfully constructed and its effect on the downregulation of miR-221/222 expression was investigated. In the present study, the dual luciferase reporter assay revealed a phosphatase and tensin homolog (PTEN) deletion on chromosome 10 to be a target gene of miR-221/222. It was also demonstrated that miR-221/222 suppression by transfection with an miR-221/222 sponge in vitro resulted in upregulation of PTEN. Notably, the proliferation and invasiveness of the miR-221/222 sponge-transfected cells was significantly inhibited, while apoptosis was promoted, when determined by Cell Counting Kit-8, Transwell assays and flow cytometry. The results of the present study prove that miR-221/222 may downregulate the expression of PTEN in OSCC cells and function as oncogenes, providing a novel insight into the underlying mechanism of OSCC tumorigenesis. The present study suggests that upregulating the expression of PTEN by downregulation of miR-221/222 may be a potential treatment for OSCC.

Bioinformatics analysis of the expression and role of microRNA-221-3p in the head and neck squamous cell carcinoma

“…In addition, a large number of valuable epidemiological studies have shown that UGT1A7 affects individuals' susceptibility to various cancers, such as pancreatic cancer [36],gastrointestinal carcinomas [37].Now our study suggests that miR-221- [38,39,40,41,42], a control the progression of the tumors. For example, miR-221-3p has be regarded as a tumor biomarker that can be used to assess the clinical prognosis of breast cancer [15]. In healthy humans, it has been shown that miR-221-3p plays a role in the process of vascular proliferation, while the tumor promoter, miR-221-3p regulates the apoptosis of tumor cells.…”

“…Recent years have seen an increasing concentration of research in, microRNA (miRNA) [10,11], which are a type of highly conserved single-stranded non-coding RNA, containing 17~22 nucleotides and are involved in the process of tumorigenesis, cell survival, and chemosensitivity [12,13,14]. They bind the 3'non-region (3'UTR) of different target mRNA (messenger RNA) genes to degrade or inhibit the mRNA translation of target genes associated with a tumor suppressor function [13,15,16]. In normal healthy individuals, miR-221-3p is observed to play a role in the process of vascular proliferation [17], while the tumor promoter, microRNA-221 is involved in the process of regulation of apoptosis of the tumor cell [18,19,20] and is associated with a variety of cancer types, including hepatocellular cancer [21], cutaneous melanoma [19], prostate cancer [20],non-small cell lung cancer [22].…”

“…Studies have shown that specific miRNA profiles can be identified between tumor tissue and adjacent healthy tissue in the HNSCC patients [2,23]. For instance, studies have reported the link between miR-211 and vascular invasion during the incidence of HNSCC [14,15,24,25,26]. However, the definite target gene of the miR-211-3p and its biological mechanism of action are still not clear.…”

MicroRNAs and small interfering RNAs as tools for the directed regulation of cellular processes for cancer therapy

“…Благодаря присутствию в их последовательности нуклеотидов участков посадки микроРНК, ýти молекулы способны выступать в роли так называемой молекулярной губки, принимающей на себя атаку микроРНК и тем самым снимающей блок с настоящей матричной РНК [46]. При помощи такой «губки» было достигнуто почти полное удаление из клетки активных miR-221/222, что повлекло за собой усиление апоптоза клеток плоскоклеточного рака ротовой полости [47].…”

Cell-Free microRNAs as Potential Oral Cancer Biomarkers: From Diagnosis to Therapy

“…These findings suggest the potential role of plasmatic miRNAs in oral carcinogenesis, as well as their high diagnostic value for early oral cancer detection. MiR-221/miR-222 cluster has been shown to promote oral carcinogenesis by downregulation of PTEN [46]. As in oral cancer, upregulated circulating miR-222 levels have been observed in a wide variety of tumors, e.g., pancreatic cancer [47] and glioma [48].…”