circ_0084927 promotes cervical carcinogenesis by sponging miR-1179 that suppresses CDK2, a cell cycle-related gene

Abstract

Background: Cervical cancer (CC) is a malignant tumor found in the lowermost part of the womb. Evolving studies on CC have reported that circRNA plays a crucial role in CC progression. In this study, we investigated the main function of a novel circRNA, circ_0084927, and its regulatory network in CC development. Methods: qRT-PCR was applied to evaluate the expression of circ_0084927, miR-1179, and CDK2 mRNA in CC tissues and cells. Dual-luciferase reporting experiments and RNA immunoprecipitation (RIP) assay were conducted to validate the target relationship of miR-1179 with circ_0084927 and CDK2 mRNA. CCK-8 and BrdU assays were also used to evaluate CC cell proliferation. The adhesion and apoptosis phenotypes of CC cells were measured using cell-matrix adhesion and caspase 3 activation assay. Flow cytometry was also employed to detect the CC cell cycle. Results: Our results indicated that circ_0084927 was up-regulated in CC tissues and cells. Findings also revealed that circ_0084927 silence inhibited CC cell proliferation and adhesion while facilitating apoptosis and triggering cell cycle arrest. However, miR-1179 down-regulation appeared in CC tissues. Apart from observing that circ_0084927 abolished miR-1179's inhibitory effects on cell proliferation and adhesion, it was found that CDK2 was up-regulated in CC tissues and was instrumental in cancer promotion. Also observed was that miR-1179 directly targeted CDK2, thereby inhibiting CDK2's promotion on the malignant phenotypes of CC cells. Lastly, results indicated that circ_0084927 revoked the inhibitory effect of miR-1179 on CDK2 by sponging miR-1179. Conclusion: circ_0084927 promoted cervical carcinogenesis by sequestering miR-1179, which directly targeted CDK2. Our results also provided novel candidate targets for CC treatment in that it revealed the circ_0084927/miR-1179/CDK2 regulatory network that strengthened CC aggressiveness.

MiR-1179 is downregulated in cervical cancer and its overexpression suppresses cancer cells invasion by targeting CHAF1A/ZEB1

“…Some researchers indicated that miR-1179 promoted cell invasion in esophageal squamous cell carcinoma (Jiang et al, 2015). MiR-1179 has been also identified as a suppressor in several cancers such as human non-small cell lung cancer (Heller et al, 2018), gastric cancer , papillary thyroid carcinoma (Ye et al, 2020) and cervical cancer (Qu et al, 2020). Interestingly, consistently with the effect of miR-1179 in other cancers, our study also supports the inhibitory role of miR-1179 in cervical cancer, as miR-1179 suppressed the cervical cancer cells invasion.…”

MEX3A knockdown inhibits the tumorigenesis of colorectal cancer via modulating CDK2 expression

“…Previous studies have shown that the expression levels of CDK2, CDK4 and CDK6 are often upregulated in various types of cancer, and are associated with tumorigenesis by interacting with other proteins ( 22 , 23 ). For example, Qu et al ( 24 ) reported that CDK2 served a key role in circular RNA (circ)_0084927/microRNA (miR)-1179 signaling axis-mediated cervical cancer development. Zhao et al ( 25 ) found that CDK6 knockdown suppressed gastric cancer cell proliferation via regulating the cell cycle.…”

Design, Synthesis, Molecular Modeling, Anticancer Studies, and Density Functional Theory Calculations of 4-(1,2,4-Triazol-3-ylsulfanylmethyl)-1,2,3-triazole Derivatives

“…Furthermore, the speed and accuracy of the molecular docking approaches have been enhanced and these methods now play a noteworthy role in structure-based drug design. The newly synthesized hybrids were gauged using in silico docking studies for acquiring an additional apprehension of the binding pattern of the target ligands with the cyclin-dependent kinase 2 (CDK2), whose overexpression causes dysfunction of the cell cycle, which is thoroughly allied with hyperproliferation of cancer cells. − Numerous evidences have been put forward in the literature sustaining the concept of restraining cancer progression by aiming CDK2. − In various categories of human tumors, the dysregulation of CDK2 is noticed, thereby for anticancer therapy, making CDK2 a promising drug target. ,− In breast cancer progression, CDK2 is considered accountable for activating and phosphorylating the receptor hormones. CDK2 structure with Protein Data Bank (PDB) ID: 2R3I was recruited for carrying out molecular docking studies owing to its higher resolution (1.28 Å) and nonmutated monomeric form.…”