miRNA-641 inhibits the proliferation, migration, and invasion and induces apoptosis of cervical cancer cells by directly targeting <em>ZEB1</em>

Abstract

BackgroundmiRNAs have been found to be dysregulated in cervical cancer. The dysregulation of miRNA has been implicated in cervical carcinogenesis and progression. Therefore, further studies of the specific roles of deregulated miRNAs in cervical cancer and underlying molecular mechanisms may facilitate the identification of novel therapeutic techniques for patients with this disease. miRNA-641 (miR-641) was previously reported to serve an important role in lung cancer. However, the expression pattern and roles of miR-641 in cervical cancer remain unclear.MethodIn this study, the expression level of miR-641 in cervical cancer tissues and cell lines was detected using RT-qPCR. The influence of miR-641 upregulation in cervical cancer cell proliferation, apoptosis, migration and invasion was evaluated using CCK-8 assay, flow cytometry assay, migration and invasion assays, respectively. In vivo tumor growth assay was utilized to determine the effect of miR-641 overexpression in the tumor growth of cervical cancer cells in vivo. The molecular mechanisms underlying the action of miR-641 in cervical cancer cells were also explored.ResultsWe found that miR-641 expression was obviously decreased in cervical cancer tissues and cell lines, which strongly correlated with the International Federation of Gynecology and Obstetrics stage and lymph node metastasis. Upregulation of miR-641 inhibited cell proliferation, induced apoptosis, and reduced metastasis in cervical cancer. Additionally, bioinformatics analysis predicted ZEB1 as a novel target gene of miR-641. Notably, luciferase reporter assay, RT-qPCR, and Western blot analysis revealed that miR-641 decreased ZEB1 expression in cervical cancer cells by directly targeting its 3′-untranslated region. Furthermore, ZEB1 was upregulated in cervical cancer tissues, which was negatively correlated with miR-641 expression. Moreover, recovered ZEB1 expression attenuated the tumor suppressive action of miR-641 overexpression in the malignant phenotypes of cervical cancer cells. Besides, miR-641 could hinder cervical cancer tumor growth in vivo by inhibiting ZEB1.ConclusionThese results indicate that miR-641 has tumor suppressive roles in the development of cervical cancer by directly targeting ZEB1, suggesting that miR-641 is a novel, effective therapeutic target for treating patients with this disease.

Circular RNA S-7 promotes ovarian cancer EMT via sponging miR-641 to up-regulate ZEB1 and MDM2

“…It has been reported that miR-641 can target MDM2 in lung cancer and serve as a tumor suppressor; miRNA-641 inhibits the growth, migration and invasiveness, prompts cervical cancer cell apoptosis via straightly targeting zeb1 [22,23]. We additional identified the considerably amplified mRNA levels of zeb1 and mdm2.…”

“…It has been reported that zeb1 and mdm2 are the downstream targets of miR-641 [22,23]; meanwhile, RNA-immunoprecipitation assay showed the direct interaction between the miR-614 and ZEB1, the miR-614 and MDM2 in both the SKOV3 and A2780 cells ( Figure 4A). To determine whether ciRS-7 sponges miR-641 to regulate zeb1 and mdm2 expression, we first determined the zeb1 and mdm2 expression levels by qRT-PCR in the OC cells.…”

The COX10-AS1/miR-641/E2F6 Feedback Loop Is Involved in the Progression of Glioma

“…Previous studies have demonstrated that miR-641 participates in the development of some tumours. For instance, Kong et al reported that miR-641 inhibits the progression of lung cancer [30]; Chen et al showed that miR-641 is involved in the erlotinib resistance of non-small-cell lung cancer [31]; and Yao et al suggested that miR-641 acts as a tumour suppressor in cervical cancer [32]. There is also a study that reported that miR-641 could target ATK2 to regulate glioma progression [33]; however, the role and mechanism of miR-641 in glioma still need further study.…”

Dissimilar Appearances Are Deceptive–Common microRNAs and Therapeutic Strategies in Liver Cancer and Melanoma

“…The discovery of RNA-interference (RNAi), a mechanism mediated by one specific family of those non-coding RNAs-so-called microRNAs (miRNAs, miRs)-was groundbreaking [2,3]. MiRNAs are involved in the regulation of all major cellular processes, including proliferation, apoptosis, cell-cycle regulation and differentiation [3][4][5][6][7][8]. Until today, more than 1800 miRNA sequences have been discovered in the human genome [9] and these Figure 1.…”