MicroRNA-195 suppresses tumor cell proliferation and metastasis by directly targeting BCOX1 in prostate carcinoma

Abstract

Elucidation of the downstream targets regulated by the metastasis-suppressive miRNAs can shed light on the metastatic processes in prostate cancer (PCa). We conducted microarray analyses and found that miR-195 was significantly decreased in metastatic PCa. Low miR-195 expression is an independent prognostic factor for poor biochemical recurrence-free and overall survival. Forced expression of miR-195 in PCa cells drastically inhibits proliferation, migration and invasion in vitro and inhibits tumor growth and metastasis in vivo. BCOX1 is identified as a direct target of miR-195 in PCa, and is found to be drastically increased in metastatic PCa. BCOX1 knockdown phenotypically copies miR-195-induced phenotypes, whereas forced expression of BCOX1 reverses the effects of miR-195. Collectively, this is the first report unveils that loss of miR-195 expression and thus uncontrolled BCOX1 upregulation might drive PCa metastasis.Electronic supplementary materialThe online version of this article (doi:10.1186/s13046-015-0209-7) contains supplementary material, which is available to authorized users.

Pro-inflammation NF-κB signaling triggers a positive feedback via enhancing cholesterol accumulation in liver cancer cells

“…MiR-195 is a member of the miR-15/16/195/424/497 family [24]. It has been reported that miR-195 suppresses cancer development and is downregulated in multiple types of cancer, such as prostate [25, 26], lung [27], osteosarcoma [28], HCCs [29], and so forth. Genome-wide screening suggests that miR-195 mediates NF-κB activity by directly targeting the expression of IKKα TAB3 in HCCs [19].…”

MicroRNA‐195‐5p suppresses osteosarcoma cell proliferation and invasion by suppressing naked cuticle homolog 1

“…This family is comprised of six members and clustered on three separate chromosomes (Porrello et al, ). Recently, several studies in cancer cell lines and tumor samples have demonstrated the down‐regulation of miR‐195‐5p in prostate cancer (Cai et al, ; Guo et al, ; Wu et al, ), lung cancer (Yongchun et al, ; Liu et al, ), breast cancer (Zhao et al, ; Singh et al, ), hepatocellular carcinoma (Qu et al, ; Xu et al, ), and osteosarcoma (Han et al, ). Given that miR‐195‐5p has been reported to be frequently downregulated in cancer and tumor cell lines, we supposed that miR‐195‐5p may function as a tumor suppressor in osteosarcoma.…”

“…miR‐195‐5p , which belongs to miR‐16/15/195/424/497 family, is regularly downregulated in numerous types of tumors, including prostate cancer (Cai et al, ; Guo et al, ; Wu et al, ), lung cancer (Yongchun et al, ; Liu et al, ), breast cancer (Zhao et al, ; Singh et al, ), hepatocellular carcinoma (Qu et al, ; Xu et al, ), and osteosarcoma (Han et al, ). Studies in tumor cell lines and tumor samples have shown that miR‐195‐5p could inhibit cell proliferation, invasion, and metastasis through regulating multiple target genes, thus functions as a tumor suppressor (Cai et al, ; Han et al, ; Liu et al, ; Wu et al, ; Xu et al, ).…”

Development of a deregulating MicroRNA panel for the detection of early relapse in postoperative colorectal cancer patients

“…Several previous studies have indicated that miR-93, miR-195, and members of the let-7 family of miRs are downregulated in lung cancer, CRC, and melanoma tissues as compared with normal tissue, suggesting that these miRs are tumor suppressors [29][30][31][32][33][34][35][36][37]. miR-93 can suppress the proliferation of human colon cancer cells and colon cancer stem cells, with worse OS being associated with low miR-93 expression in CRC patients [37,38].…”

“…miR-93 can suppress the proliferation of human colon cancer cells and colon cancer stem cells, with worse OS being associated with low miR-93 expression in CRC patients [37,38]. miR-195 can suppress tumor cell proliferation and metastasis by targeting several proteins, including BCOX1, BCL-2, and CARMA3 [32][33][34]. The overexpression of let-7b in vitro can downregulate cell-cycle-related proteins, including cyclin D1, cyclin D3, cyclin-dependent kinase 4, and the high-mobility group protein and oncogene [30,39].…”