miR-486 Promotes the Invasion and Cell Cycle Progression of Ovarian Cancer Cells by Targeting CADM1

Abstract

Objective. To explore the role and possible underlying mechanism of miR-486 in ovarian cancer (OC) cells. Methods. The expression of miR-486 and CADM1 was detected by qRT-PCR in OC tissues and adjacent nontumor tissues and OC cell lines. The dual-luciferase reporter gene system was used to determine the targeting relationship between miR-486 and CADM1. CCK-8, colony formation assay, Transwell, and flow cytometry were performed to detect cell proliferation, cell invasion, cell cycle progression, and the apoptotic cell death, respectively. Western blot was carried out to detect the expression of CADM1 protein and the proteins associated with cell cycle progression. Results. miR-486 was significantly upregulated in OC tissues and cells, while CADM1 expression was significantly downregulated. Dual-luciferase reporter assays further confirmed that CADM1 was a target gene of miR-486. Interference with miR-486 could inhibit the proliferation and invasion and promoted the apoptosis of SKOV3 cells. Knocking down both miR-486 and CADM1 significantly increased the SKOV3 cell proliferation, invasion, and the number of cells transitioning from the G0/G1 phase into the S phase of cell cycle and reduced the cellular apoptosis. Western blot analysis revealed that the expression of cell cycle progression-related proteins (CyclinD1, CyclinE, and CDK6) was significantly reduced, and the p21 expression was increased when interfering with both miR-486 and CADM1 expression. Conclusion. Our results suggested that miR-486 could act as a tumor promoter by targeting CADM1 and be a potential therapeutic target for the treatment of OC.

Construction of atrial fibrillation‐related circRNA/lncRNA‐miRNA‐mRNA regulatory network and analysis of potential biomarkers

“…Xiong et al 26 showed that XIST can act on miR‐486‐5p to regulate brain ischemia–reperfusion injury. In addition, miR‐486 could participate in the biological functions of ovarian cancer cells by interacting with CADM1 in an ovarian cancer study 27 . Based on our network, XIST/circRNA_2773‐miR‐486‐5p‐CADM1 and other related pathways involved in the occurrence and development of AF, the down‐regulated XIST, circRNA_2773, and CADM1 were negatively correlated with miR‐486‐5p expression and had a targeting relationship with miR‐486‐5p.…”

“…In addition, miR‐486 could participate in the biological functions of ovarian cancer cells by interacting with CADM1 in an ovarian cancer study. 27 Based on our network, XIST/circRNA_2773‐miR‐486‐5p‐CADM1 and other related pathways involved in the occurrence and development of AF, the down‐regulated XIST, circRNA_2773, and CADM1 were negatively correlated with miR‐486‐5p expression and had a targeting relationship with miR‐486‐5p. That is, XIST/circRNA_2773 could competitively bind miR‐486‐5p to act as a “sponge,” thus diminishing the inhibitory effect of miR‐486‐5p on CADM1.…”

“…In addition, miR-486 could participate in the biological functions of ovarian cancer cells by interacting with CADM1 in an ovarian cancer study. 27 has-miR-149-5p to promote IL-6 release. 32 Another study on chronic obstructive pulmonary disease reported that IL6-AS1 (lncRNA) can competitively bind to miR-149-5p to promote the expression of IL-6.…”

Analysis of the key ligand receptor CADM1_CADM1 in the regulation of thyroid cancer based on scRNA-seq and bulk RNA-seq data

“…At present, large number of DNMT inhibitor candidates which can inhibit DNA methylation are in the developmental pipeline and some are currently in clinical trials ( 49 ). Although there is no study on increasing the expression of CADM1 through regulating associated miRNAs in PTC up to now, there are some studies on other cancers: inhibiting microRNA-1246 can increase the expression of CADM1 in hepatocellular carcinoma ( 50 ); upregulating miR-486 can downregulate CADM1 expression in Ovarian Cancer ( 51 ); miR-155-3p could downregulate expression of CADM1 in breast cancer ( 33 ). Thus, more researches are needed to explore related miRNAs in PTC.…”

Characterization of EGFR-reprogrammable temozolomide-resistant cells in a model of glioblastoma

“…They further found that inhibiting the miRNA not only increased the expression of CADM1 but inhibited activation of the STAT3 pathway, a determinant of GBM proliferation and tumorgenicity. A similar study in ovarian cancer cells described the downregulation of the CADM1-targeting miR-486, which saw reduced cell viability, proliferation, and an increased proportion of cells in G0/G1 arrest [ 49 ]. Moreover, CADM1 was inversely proportional to the expression of cyclin D1, cyclin E, CDK6, and p21.…”