MicroRNA‐26a‐5p inhibits breast cancer cell growth by suppressing RNF6 expression

Abstract

MicroRNA-26a-5p (miR-26a-5p) has been reported to be involved in the tumorigenesis of several tumors, but its function in breast cancer is still unknown. In this study, miR-26a-5p was found significantly downregulated in both of the breast cancer tissues and cell lines, and low expression of miR-26a-5p predicted a poor prognosis for breast cancer patients. Overexpression of miR-26a-5p could significantly inhibit breast cancer cell growth. Further studies revealed that overexpression of miR-26a-5p downregulated the protein levels of Cyclin D1, CDK4, and CDK6, but upregulated the expression levels of p21, p27, and p53. In mechanism, miR-26a-5p targeted the 3 0 UTR of ring finger protein 6 (RNF6) mRNA and inhibited RNF6 expression in breast cancer cells.Moreover, overexpression of miR-26a-5p inhibited RNF6/ERα/Bcl-xL axis in breast cancer cells. In contrast, inhibiting miR-26a-5p upregulated RNF6/ERα/Bcl-xL axis.Further studies indicated that miR-26a-5p mediated RNF6/ERα/Bcl-xL axis through regulating the stability of ERα protein. Collectively, downregulation of miR-26a-5p plays essential roles in breast cancer by mediating RNF6/ERα/Bcl-xL axis, which might provide important implications for the therapeutics of breast cancer.

RNF6 as an Oncogene and Potential Therapeutic Target—A Review

“…The authors who studied breast cancer have reached similar conclusions [7,12]. The expression of the RNF6 was high in both primary breast cancer cells and cell lines.…”

“…Thanks to its function and involvement in many cancers' pathogenesis, the RNF6 may be a molecular target in cancer therapy. Research is currently conducted with various RNF6 expression inhibitors or compounds that inhibit the activation of RNF6 protein-dependent signaling pathways [10][11][12][13]. There is a large group of proteins with a RING finger domain, but RNF6 has not been fully described [14].…”

Potential miRNAs for miRNA-Based Therapeutics in Breast Cancer

“…Briefly, these four ts-miRNAs could interact with multiple protein partners and suppress the oncogenic properties of breast cancers; 1) miR-26a binds to RNF6 [ 53 ], CHD1 [ 54 ], GREB1 [ 54 ], KPNA2 [ 54 ], metadherin [ 55 ] and MCL-1 [ 56 ], 2) miR-193a/b to DDAH1 [ 172 ], PTP1B [ 173 ], MORC4 [ 174 ], WT1 [ 175 ], RAB22A [ 176 ], uPA [ 178 ], 3) miR-216a/b to TLR4 [ 194 ], PKC-α [ 195 ], PAK2 [ 196 ], SDCBP [ 197 ], P2X7R [ 198 ] and HDAC8 [ 199 ] and 4) miR223 to caprin-1 [ 203 ] and STAT5A [ 206 ]. Particularly, miR-26a, miR-193a/b and miR-223 could re-sensitize breast cancer cell lines to chemotherapeutic drugs.…”

“… Roles of miRNAs. Summary of all the articles published from 2018 to 2020 in PubMed Database [ 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 , 65 , 66 , 67 , 68 , 69 , 70 , 71 , 72 , 73 , 74 , 75 , 76 , 77 , 78 , 79 , 80 , 81 , 82 , 83 , 84 , 85 , …”

MSCs‑derived exosomes attenuate ischemia-reperfusion brain injury and inhibit microglia apoptosis via exosomal miR-26a-5p mediated suppression of CDK6

“…Interestingly, Huang et al found that miR-26a-5p inhibits the growth of breast cancer cells by downregulating the expression of CDK6 (20), suggesting that CDK6 might be a direct or indirect downstream gene. Meanwhile, a miRNA pro ling and bioinformatics prediction performed by Canturk et at.…”