Relevance of miR-21 in regulation of tumor suppressor gene PTEN in human cervical cancer cells

Abstract

BackgroundExpression of the microRNA miR-21 has been found to be altered in almost all types of cancers and it has been classified as an oncogenic microRNA or oncomir. Due to the critical functions of its target proteins in various signaling pathways, miR-21 is an attractive target for genetic and pharmacological modulation in various cancers. Cervical cancer is the second most common cause of death from cancer in women worldwide and persistent HPV infection is the main etiologic agent. This malignancy merits special attention for the development of new treatment strategies. In the present study we analyze the role of miR-21 in cervical cancer cells.MethodsTo identify the downstream cellular target genes of upstream miR-21, we silenced endogenous miR-21 expression in a cervical intraepithelial neoplasia-derived cell lines using siRNAs. The effect of miR-21 on gene expression was assessed in cervical cancer cells transfected with the siRNA expression plasmid pSIMIR21. We identified the tumor suppressor gene PTEN as a target of miR-21 and determined the mechanism of its regulation throughout reporter construct plasmids. Using this model, we analyzed the expression of miR-21 and PTEN as well as functional effects such as autophagy and apoptosis induction.ResultsIn SiHa cells, there was an inverse correlation between miR-21 expression and PTEN mRNA level as well as PTEN protein expression in cervical cancer cells. Transfection with the pSIMIR21 plasmid increased luciferase reporter activity in construct plasmids containing the PTEN-3′-UTR microRNA response elements MRE21-1 and MRE21-2. The role of miR-21 in cell proliferation was also analyzed in SiHa and HeLa cells transfected with the pSIMIR21 plasmid, and tumor cells exhibited markedly reduced cell proliferation along with autophagy and apoptosis induction.ConclusionsWe conclude that miR-21 post-transcriptionally down-regulates the expression of PTEN to promote cell proliferation and cervical cancer cell survival. Therefore, it may be a potential therapeutic target in gene therapy for cervical cancer.

Evaluation of Expression of 4 Mirnas in Cytological Samples as an Additional Method of Cervical Cancer Diagnosis

“…Таким обра-зом, было выбрано 18 молекул микроРНК, так назы-ваемых «потенциально маркерных» микроРНК: miR-106 [21,24], miR-1246 [25,26], miR-125b [27][28][29], miR-126 [30][31][32], miR-145 [33,34], miR-146a [35,36], miR-146b [37], miR-155 [38,39], miR-192 [40], miR196b [41], miR-200b [42,43], miR-203 [44,45], miR-20a [46], miR-21 [47,48], miR-31 [49]; miR-34a [27,50]; miR-375 [51,52], miR-99a [53]. Их участие в церви-кальном канцерогенезе было подтверждено как мини-мум в 2 независимых исследованиях.…”

lncRNA DLG1-AS1 Promotes Cell Proliferation by Competitively Binding with miR-107 and Up-Regulating ZHX1 Expression in Cervical Cancer

“…Studies have shown that the abnormal expression of microRNAs (miRNAs) plays an important role in the occurrence, progression, diagnosis, treatment, and prognosis of most tumors, including cervical cancer [3,4]. miRNAs are a type of small non-coding singlestranded RNA that can bind to the 3′-untranslated region (UTR) of target gene mRNA via complementary base pairing, inhibiting the degradation or translation of target gene mRNA, regulating gene expression at the post-transcriptional level, and participating in the regulation of cellular processes, such as inflammatory and stress responses, differentiation, apoptosis, and migration [5][6][7].…”

Differential Expression of MicroRNAs in Uterine Cervical Cancer and Its Implications in Carcinogenesis; An Integrative Approach

“…26 A recent study identified up-regulation of miR-21 in cervical cancer, which in turn down-regulates the expression of PTEN and promotes cell proliferation and cell survival. 27 Little is known about the expression of miR-135b in cervical cancer. Down-regulation of miR-135b markedly inhibited proliferation and arrested cell cycle in cervical cancer cells.…”