miR-218-5p/RUNX2 Axis Positively Regulates Proliferation and Is Associated with Poor Prognosis in Cervical Cancer

Abstract

The overexpression of miR-218-5p in cervical cancer (CC) cell lines decreases migration, invasion and proliferation. The objective was to identify target genes of miR-218-5p and the signaling pathways and cellular processes that they regulate. The relationship between the expression of miR-218-5p and RUNX2 and overall survival in CC as well as the effect of the exogenous overexpression of miR-218-5p on the level of RUNX2 were analyzed. The target gene prediction of miR-218-5p was performed in TargetScan, miRTarBase and miRDB. Predicted target genes were subjected to gene ontology (GO) and pathway enrichment analysis using the Kyoto Encyclopaedia of Genes and Genomes (KEGG). The miR-218-5p mimetic was transfected into C-33A and CaSki cells, and the miR-218-5p and RUNX2 levels were determined by RT–qPCR. Of the 118 predicted targets for miR-218-5p, 86 are involved in protein binding, and 10, including RUNX2, are involved in the upregulation of proliferation. Low miR-218-5p expression and a high level of RUNX2 are related to poor prognosis in CC. miR-218-5p overexpression is related to decreased RUNX2 expression in C-33A and CaSki cells. miR-218-5p may regulate RUNX2, and both molecules may be prognostic markers in CC.

RUNX transcription factors: biological functions and implications in cancer

“…In a parallel investigation, Onodera et al scrutinized 137 cases of invasive ductal carcinoma of the breast through immunohistochemical staining and documented overexpression of RUNX2 [ 66 ]. Concurrently, elevated levels of RUNX2 in cervical cancer were found to be associated with decreased miR-218-5p expression, and this high expression of RUNX2 positively regulated cervical cancer cell proliferation [ 67 ].Wang et al found that MRE11 plays a pro-cancer role in oral cancer through the RUNX2/CXCR4/AKT/FOXA2 signaling axis, and both MRE1 and RUNX2 have been shown to be highly expressed in oral cancer samples [ 68 ]. Sancisi et al demonstrated that RUNX2 expression is reactivated in thyroid and breast cancers [ 69 ].…”

“…Elevated levels of RUNX2 consistently serve as an adverse prognostic marker across multiple cancer types. For instance, in cervical cancer, high RUNX2 expression correlates with poor prognosis, and both RUNX2 and its inhibitory counterpart, miR-218-5p, are identified as potential prognostic markers [ 67 ]. Research by Li et al indicated that the upregulation of RUNX2 in EOC is likely associated with tumor progression and unfavorable outcomes [ 104 ].…”

RUNX2 and Cancer

“…Consistent results with these were obtained by Western blot analysis of 10 paired cancer and normal tissues [ 17 ]. RUNX2 protein was detected in cervical cancer tissues, and RUNX2 expression declined upon overexpression of miR-218-5p in C-33A and CaSki cells [ 58 ]. RUNX2 protein was elevated in human thyroid cancer cell lines and cancer tissues compared with primary cell lines and normal thyroid tissues [ 10 ].…”