Up-Regulation of Long Noncoding RNA SRA Promotes Cell Growth, Inhibits Cell Apoptosis, and Induces Secretion of Estradiol and Progesterone in Ovarian Granular Cells of Mice

Abstract

BackgroundIncreasing evidence indicates that long noncoding RNAs (LncRNAs) play a key role in multiple pathological processes. It has been shown that LncRNA steroid receptor RNA activator (SRA) is elevated in peripheral blood of patients with polycystic ovary syndrome (PCOS). The aim of this study was to assess the effect of elevated LncRNA SRA on ovarian granular cells of mice in vitro.Material/MethodsWe firstly isolated granular cells from mouse ovaries and over-expressed the LncRNA SRA by means of lentiviral transfection in this cell line. Then, we assessed the effects of LncRNA SRA on granular cells through real-time PCR, CCK-8 assay, flow cytometry, Hoechst staining, and Western blot assay.ResultsWe demonstrated that elevated LncRNA SRA stimulated cell growth, changed distribution of cell cycle phases with increase of Cyclin B, Cyclin E, and Cyclin D1, and inhibited cell apoptosis with up-regulation of bcl2 and down-regulation of bax, cleaved-caspase 3, and cleaved-PARP. Moreover, the contents of estradiol (E2) and progesterone (PG) and expressions of their key enzymes (CYP19A1 and CYP11A1) were up-regulated following over-expression of LncRNA SRA.ConclusionsTaken together, our results indicate that abnormal LncRNA SRA may be a risk factor for evoking PCOS.

Steroid Receptor RNA Activator, a Long Noncoding RNA, Activates p38, Facilitates Epithelial-Mesenchymal Transformation, and Mediates Experimental Melanoma Metastasis

“…It was reported that SRA/SRAP depletion and SRAP overexpression lead respectively to a decrease and an increase in breast cancer cell motility (Yan et al, 2015). SRA was found to be increased in several other tumors, including hepatoma (Luo et al, 2017), ovarian cancers (Li et al, 2018), and cervical cancers (Eoh et al, 2017). Again, none of these studies utilized an in vivo metastasis model to address and validate the important role of SRA in cancer metastasis.…”

Effects of Castration on miRNA, lncRNA, and mRNA Profiles in Mice Thymus

“…Long non-coding RNAs (lncRNAs) are important components of non-coding RNAs [24]. lncRNAs can regulate the expression of target genes in a variety of ways, such as cis, trans, or combined with miRNAs, so it is not easy to determine their target genes [25,26].…”

“…The roles of lncRNAs in organ development, cancer treatment, and aging have been widely reported over the past decades [27][28][29]. In addition, Hu et al found that lncRNAs play an important role in the differentiation of T helper subsets [30]; Li et al found that the levels of 17β-estradiol (E2) and progesterone in mice ovarian cells increased after overexpression of lncRNA SRA [24]. A recent study found that androgen and estrogen influence lncRNA expression during penis development in marsupials [31].…”

Targeting steroid receptor RNA activator (SRA), a long non-coding RNA, enhances melanogenesis through activation of TRP1 and inhibition of p38 phosphorylation

“…In addition, SRA was also found to contribute to several pathological processes, including obesity, tumorigenesis, and cardiomyopathy [15]. Specifically in the process of tumorigenesis, SRA was reported to be actively involved in the progression of benign tumors and malignant cancers that are related to steroid or sex hormones, including ovarian endometriosis [16], polycystic ovary [17], uterine myoma [18], as well as endocrine cancers, breast cancers, ovarian cancers [19], and cervical cancers [20]. Because some pigmentary diseases have gender differences, for example, melasma preferentially affects woman, we remain interested whether SRA, which helps regulate cellular pathways related to steroid or sex hormone, regulates melanogenesis in melanocytes.…”