Arm Selection Preference of MicroRNA-193a Varies in Breast Cancer

Abstract

MicroRNAs (miRNAs) are short noncoding RNAs derived from the 3′ and 5′ ends of the same precursor. However, the biological function and mechanism of miRNA arm expression preference remain unclear in breast cancer. We found significant decreases in the expression levels of miR-193a-5p but no significant differences in those of miR-193a-3p in breast cancer. MiR-193a-3p suppressed breast cancer cell growth and migration and invasion abilities, whereas miR-193a-5p suppressed cell growth but did not influence cell motility. Furthermore, NLN and CCND1, PLAU, and SEPN1 were directly targeted by miR-193a-5p and miR-193a-3p, respectively, in breast cancer cells. The endogenous levels of miR-193a-5p and miR-193a-3p were significantly increased by transfecting breast cancer cells with the 3′UTR of their direct targets. Comprehensive analysis of The Cancer Genome Atlas database revealed significant differences in the arm expression preferences of several miRNAs between breast cancer and adjacent normal tissues. Our results collectively indicate that the arm expression preference phenomenon may be attributable to the target gene amount during breast cancer progression. The miRNA arm expression preference may be a means of modulating miRNA function, further complicating the mRNA regulatory network. Our findings provide a new insight into miRNA regulation and an application for breast cancer therapy.

Emerging genotype–phenotype relationships in patients with large NF1 deletions

“…One of these, MIR193A, encodes two mature miRNAs with well-known tumour suppressor functions; miR193a-3p and miR193a-5p are generated from the primary transcript by means of several maturation steps. The expression preference of miR193a-5p and miR193a-3p is likely to be determined by the Ago protein (reviewed by Tsai et al 2016). According to the mirbase database (http://www.mirbase.org/), miR193a-3p is more abundantly expressed in human tissues than miR193a-5p.…”

“…According to the mirbase database (http://www.mirbase.org/), miR193a-3p is more abundantly expressed in human tissues than miR193a-5p. Several studies have indicated that miR193a-3p suppresses tumour development by silencing multiple target genes including SRSF2 , HIC2, HOXC9, PSEN1, LOXL4, ING5 , KIT , PLAU and MCL1 (Tsai et al 2016). miR193a-3p has been found to be down-regulated by hypermethylation in oral squamous cell carcinoma cell lines (Kozaki et al 2008), non-small cell lung cancer (Heller et al 2012; Wang et al 2013; Liang et al 2015; Ren et al 2015), bladder cancer (Deng et al 2014; Lv et al 2014; Li et al 2015), hepatocellular carcinoma (Salvi et al 2013), BRAF mutation-positive malignant melanoma (Caramuta et al 2010), acute myeloid leukaemia (Xing et al 2015) and pleural mesothelioma (Williams et al 2015).…”

“…However, it is unclear whether the down-regulation of miR193a-3p is a cause or a consequence of tumorigenesis. Decreased expression of miR193a-3p has been found to be correlated with metastasis, apoptosis and proliferation in breast cancer cell lines (Iliopoulos et al 2011; Tsai et al 2016) and ovarian tumour tissue (Nakano et al. 2013).…”

MiR-193a-3p is an Important Tumour Suppressor in Lung Cancer and Directly Targets KRAS

“…miR-193a, which consists of miR-193a-3p and miR-193a-5p, is one of the miRNAs involved in carcinogenesis. miR-193a-3p plays essential roles in the multi-chemoresistance of bladder cancer [10], epithelial ovarian cancer [11], breast cancer [12], colorectal cancer [13] and lung cancer [14]. However, although several studies indicating that miR-193a-3p is closely related to tumourigenesis have been published, the detailed roles of miR-193a-3p in the initiation and progression of NSCLC remain largely unknown.…”

Varying miR-193b-3p Expression Patterns in Breast Cancer Cell Lines Indicates Its Potential for Cancer Management Strategies

“…This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International License (http://creativecommons.org/licenses/by-nc/4.0/) which permits copy and redistribute the material just in noncommercial usages, provided the original work is properly cited analysis software revealed that miR-193b targets 5genes in Wnt and TGF-b signaling pathways (11)(12)(13)(14). Although miR193b sequence shares 88% identity with miR-193a, it is encoded by a separate gene with distinct regulation (15,16). miR-193b has been implicated as a tumor suppressor in breast cancer.…”