miR-182 modulates cell proliferation and invasion in prostate cancer via targeting ST6GALNAC5

Abstract

Altered expression of miR-182 has been observed in various types of human cancer. The purpose of this study was to investigate the expression of miR-182 and its role in prostate cancer (PCa). Expression of miR-182 and ST6GALNAC5 in tumor tissues and the Du145 PCa cell line was analyzed. Cell proliferation assay, colony formation assay, transwell assay, and wound healing assay were performed. The impact of miR-182 on tumor growth was investigated using a xenograft model. The results indicated that expression of miR-182 was higher in PCa tissues and cell lines, while ST6GALNAC5 was decreased. Downregulating miR-182 significantly inhibited the capacities of proliferation and invasion of PC3 and Du145 cells. ST6GALNAC5 was demonstrated to be a target of miR-182 by luciferase assay, and western blot results indicated PI3K/Akt pathway was involved in miR-182 associated effects on PC3 and Du145 cells. The animal experiment suggested that knockdown of miR-182 inhibited tumor growth. Our study proved that miR-182 participated in the proliferation and invasion of PCa cells via mediating expression of ST6GALNAC5 and established a miR-182/ST6GALNAC5/PI3K/AKT axis in regulation of tumor progression. Our investigation provided a basis for further exploration of the application of miR-182 or ST6GALNAC5associated therapies for PCa patients.

MiR-182-5p Modulates Prostate Cancer Aggressive Phenotypes by Targeting EMT Associated Pathways

“…However, it confirms the association of cell adhesion with cell proliferation and migration capabilities in tumor cells [ 42 , 43 ] and the direct regulation of these phenotypes by miR-182-5p. Similar findings in cell adhesion, migration, and invasion were observed in other PCa cells studies [ 12 , 14 , 16 , 18 , 44 , 45 ] and in other tumor models [ 32 , 46 , 47 ]. Altogether, these results support the oncomiR function of miR-182-5p in regulating cell proliferation, adhesion, and migration of PCa cells, which largely determines their tumorigenic capacity and the observed unfavorable outcome in PCa clinical cases that present with miR-182-5p overexpression [ 8 , 9 , 10 , 12 , 13 , 14 , 15 , 45 ].…”

“…This oncomiR mode of action in cell proliferation was also observed in other PCa studies. Hirata et al [ 14 ] and Bai et al [ 18 ], in an analysis of the same PCa cells as this study, reported reduced cell proliferation with the inhibition of miR-182-5p expression. Reversely, Yao et al [ 12 ], showed that miR-182-5p overexpression promoted the growth and progression of prostate cancer tumors in in vitro and in vivo models.…”

“…MiR-182-5p specifically, has been shown to be overexpressed in PCa tissues [ 8 , 9 , 10 , 11 , 12 ] in association with tumor progression and decrease in survival rates [ 10 , 13 , 14 , 15 ]. In PCa cell models, deregulation of miR-182-5p has been shown to significantly impact cell proliferation, colony formation, migration, and invasion [ 12 , 14 , 16 , 17 , 18 ].…”

Identification and comprehensive analysis of circRNA–miRNA–mRNA regulatory networks in osteoarthritis

“…MiR-30c has also recently been considered as a suppressor of bone gamma-carboxyglutamate protein ( BGLAP ) in osteogenesis ( 50 ). Target DEGs of miR-30c in our analysis were mostly related to the anti-apoptosis of abnormal tumor cells, including MAP3K9 in lung cancer ( 46 ), ST6GALNAC5 in prostate cancer ( 51 ), CSRNP3 in clear renal cell carcinoma ( 52 ), ZNF703 in breast tumors ( 53 ), and CLSPN in brain tumors ( 54 ). Thus, upregulation of hsa_circ_0102564 might help reveal the downstream mechanism involved in the abnormal maturation and proliferation of chondrocytes in OA.…”

Emerging roles of mesenchymal stem cell-derived exosomes in gastrointestinal cancers

“…Recent studies have shown that a variety of exosomal miRNAs, lncRNAs, miRNAs, and circRNAs can be used as clinical diagnostic biomarkers for GBC ( Xue et al, 2020 ; Ren et al, 2021 ; Ueta et al, 2021 ). These include miR-182, which has been found to be associated with a wide range of cancers including breast, nasopharyngeal, prostate, and glioma ( Liu et al, 2020b ; Bai et al, 2021 ; He et al, 2021 ; Ma et al, 2022 ). Zheng et al ( Zheng et al, 2020 )found that exosomal miR-182 significantly promoted the migration and invasion of GBC cells by inhibiting reversion-inducing-cysteine-rich protein with kazal motifs (RECK).…”