MiR-21 is involved in cervical squamous cell tumorigenesis and regulates CCL20

Abstract

MicroRNA 21 (miR-21) has been implicated in various aspects of carcinogenesis. However, its function and molecular mechanism in cervical squamous carcinoma have not been studied. Using TaqMan quantitative real-time PCR and Northern blot, we confirmed that miR-21 is significantly overexpressed in human cervical squamous cancer tissues and cell lines. Remarkably, we showed that the level of miR-21 correlates with the tumor differentiation and nodal status by ISH. Furthermore, we demonstrated that miR-21 regulates proliferation, apoptosis, and migration of HPV16-positive cervical squamous cells. In order to identify candidate target genes for miR-21, we used gene expression profiling. By luciferase reporter assays, we confirmed that CCL20 is one of its target genes, which is related to the HPV16 E6 and E7 oncogenes. Our results suggest that miR-21 may be involved in cervical squamous cell tumorigenesis.

Long noncoding RNA MEG3 is downregulated in cervical cancer and affects cell proliferation and apoptosis by regulating miR-21

“…24 Although MEG3 has been reported involved in the development of cervical cancer, 20 the interaction between MEG3 and miRNAs in cervical cancer is still not verified. In our previous study, we found that miR-21-5p was correlated with lymph nodes metastasis, HR-HPV infection, cell proliferation and apoptosis in cervical cancer, 13 which is similar to MEG3. Therefore, we would like to explore the interaction between MEG3 and miR-21-5p in cervical cancer.…”

“…12 Our previous study has found that miR-21 effected tumorigenesis by regulating CCL20 in cervical squamous cell. 13 Other studies also observe that miR-21 is an oncomiR in cervical cancer, which promotes cell proliferation by downregulating the expression of programmed cell death 4 (PDCD4), 14 or by mediating aberrant STAT3 signaling. 15 In addition, miR-21 is significantly upregulated in HR-HPV positive cervical cancer.…”

The microRNA-302-367 cluster suppresses the proliferation of cervical carcinoma cells through the novel target AKT1

“…Increasing evidence indicates that miRNAs regulate diverse cellular processes, and some miRNAs have been shown to function as either tumor suppressors or oncogenes (EsquelaKerscher and Slack 2006). MiR-21, commonly considered to be an oncogene, is overexpressed in many solid tumors and has been reported to be associated with tumor progression, poor survival, and drug resistance through its interactions with PDCD4, PTEN, and CCL20 (Connolly et al 2008;Yamamichi et al 2009;Bao et al 2011;Gaur et al 2011;Gong et al 2011;Yao and Lin 2012). The tumor suppressor Let-7, a miRNA that is frequently dysregulated in lung cancer, negatively regulates RAS, HMGA2, CDK6, and CDC25A (Johnson et al 2005(Johnson et al , 2007Lee and Dutta 2007).…”

Genetic and Methylation-Induced Loss of miR-181a2/181b2 within chr9q33.3 Facilitates Tumor Growth of Cervical Cancer through the PIK3R3/Akt/FoxO Signaling Pathway

“…Although once considered to represent transcriptional "noise," the posttranscriptional regulator microRNAs (miRNAs) are now recognized to have crucial roles in the pathogenesis of cervical cancer based on the expression of dysreulation (11), such as miR-21, -133b, -138, and so on (12)(13)(14). Of special interest, given that over 50% of miRNAs are located at fragile sites and aberrant regions of chromosomes involved in cancer (15), breakpoint-associated miRNAs might contribute a new insight for considering the causal role of fragile sites in cancer development (16).…”