Suppression of MicroRNA-144 Promotes CXCR4 and CXCL12 Expression and Downregulates Apoptosis in Ovarian Cancer Cells

Abstract

MicroRNAs are important regulators in the growth and metastasis of ovarian cancers. Many assays were established to identify the role of miR-144-3p in ovarian cancer cells and its interaction with COX-2 and chemokines (CXCR4 and CXCL12). The ovarian cancer cells (OVCAR-3 and SKOV-3) were transfected with Anti-miR-144 to downregulate the miR-144-3p and cultured for 36 h. We herein examined the cell viability, colony formation, cell migration, COX-2 reporter activity, the protein expressions of CXCR4, CXCL12, COX-2, VEGF, Caspase-3, BAX and Bcl-2. We have observed that the suppression of miR-144-3p significantly increased the cell proliferation and migration and decreased the apoptosis. Moreover, the downregulation of miR-144-3p markedly increased the COX-2, CXCR4, CXCL12 and VEGF expression in OVCAR-3 and SKOV-3 ovarian cancer cells. In conclusion, miR-144-3p may play important roles in the regulation of chemokine receptor CXCR4 and its ligand CXCL12 in the progressive ovarian tumors expressing COX2. These data suggests that miR-144 has the novel therapeutic targets for the cancer therapy and cancer prevention.

Acetylation of interferon regulatory factor‐5 suppresses androgen receptor and downregulates expression of Sox2

“…Cellular proteins were denatured with SDS‐sample buffer, and 25 μg protein was resolved in each well in SDS‐PAGE gels. Western blot analysis has been described by our group 19,20 . In these experiments, specific primary antibodies (IRF5, AR, Sox2, Nanog, Oct4, CREB, p300, Ac‐Lys, PSA, β‐actin, Santa Cruz Biotechnology) were used protein expression detection.…”

“…A total of 36 hours post‐transfection, the total RNA was isolated from the transfected cells using the RNA extraction kit (Invitrogen) according to the manufacturer's recommendations. Isolation of RNA was amplified to cDNA for qRT‐PCR, steps previously described 20,21 . qRT‐PCR was carried out on ABI‐SteponePlus (LifeTechnologies, Carlsbad, California) using IRF5, Nanog, Oct4, Sox2, PSA and GAPDH primers from KiCqStart Sigma.…”

Biological Role of Tumor/Stromal CXCR4-CXCL12-CXCR7 in MITO16A/MaNGO-OV2 Advanced Ovarian Cancer Patients

“…CXCR4 participates in the EOC development [ 11 ], is expressed by ovarian cancer, tumor and stromal cells (myeloid or T cells), and cooperates with angiogenic factors to generate new vessels [ 12 ]. Silencing CXCR4 in human ovarian cancer cells reduces cell proliferation, migration and invasion and significantly decreases in vivo tumor development [ 11 , 13 ]. The only FDA-approved CXCR4 antagonist, AMD3100, sensitizes ovarian cancer to chemotherapy [ 14 ] and impairs the epithelial–mesenchymal transition (EMT) when coupled with paclitaxel (PTX)-loaded bovine serum albumin (BSA) nanoparticles [ 15 , 16 ].…”