Emerging Role of Long Non-Coding RNA SOX2OT in SOX2 Regulation in Breast Cancer

Abstract

The transcription factor SOX2 is essential for maintaining pluripotency in a variety of stem cells. It has important functions during embryonic development, is involved in cancer stem cell maintenance, and is often deregulated in cancer. The mechanism of SOX2 regulation has yet to be clarified, but the SOX2 gene lies in an intron of a long multi-exon non-coding RNA called SOX2 overlapping transcript (SOX2OT). Here, we show that the expression of SOX2 and SOX2OT is concordant in breast cancer, differentially expressed in estrogen receptor positive and negative breast cancer samples and that both are up-regulated in suspension culture conditions that favor growth of stem cell phenotypes. Importantly, ectopic expression of SOX2OT led to an almost 20-fold increase in SOX2 expression, together with a reduced proliferation and increased breast cancer cell anchorage-independent growth. We propose that SOX2OT plays a key role in the induction and/or maintenance of SOX2 expression in breast cancer.

Long non-coding RNA SOX2OT promotes cell proliferation and motility in human ovarian cancer

“…Notably, the epithelial marker (E-cadherin) was increased, while the mesenchymal marker (N-cadherin) was decreased by knockdown of SOX2OT. The impact of SOX2OT expression on EMT has been reported previously (15,16,18). EMT and its reverse process, mesenchymal-epithelial transition are both critical for embryonic development (21).…”

“…The gene does not contain open reading frames, however, it is spliced into several transcripts that are microRNA-like (14). The concurrent expression pattern between lncRNA, SOX2OT and SOX2 in certain types of human cancer and human stem cells indicates the possibility that they may be involved in specific similar signaling pathways and engage in co-regulation, which has been validated by some recent studies (15)(16)(17). SOX2OT was postulated to participate in SOX2 transcription, acting as an important enhancer (14).…”

“…Functionally, the lncRNA, SOX2OT, has a significant role in tumorigenesis. In 2014, Askarian-Amiri et al (15) investigated the regulatory effects of SOX2OT in human breast cancer, and the concordant role of SOX2OT and SOX2 was revealed. Furthermore, this study demonstrated that SOX2OT reduced cell proliferation; however, increased breast cancer cell anchorage-independent growth was detected, indicating that SOX2OT functions as a positive regulator of breast cancer.…”

Roles of lncRNA in breast cancer

“…Both SOX2 and SOX2OT are upregulated in cancer stem like cells, and SOX2 is one of key genes in maintaining pluriopotency (74). Furthermore, ectopic expression of SOX2OT leads to dramatic increase in SOX2 expression and subsequent increase in breast cancer anchorageindependent growth (73). These results indicate the potential oncogenic role of SOX2OT in breast cancer by inducing or maintaining the expression of SOX2.…”

Long non-coding RNA SOX21-AS1 modulates breast cancer stem cells properties and carcinogenesis via targeting SOX2

“…For example, in human prostate cancer stem cells, lncRNA-ROR and Oct4 mRNA both contain miR-145 binding sites and Oct4 and lncRNA-ROR directly compete for microRNA binding, activating the derepression of core transcription factors Oct4 [10]. In breast cancer, lncRNA SOX2OT is aberrantly over-expressed and led to an increased expression of SOX2, playing a key role in the maintenance of stem cell phenotypes [11]. LncRNA HOTAIR is highly upregulated in both CSC-MCF7 and CSC-MB231 cells and HOTAIR tightly regulates the proliferation, colony formation, migration and self-renewal capacity of CSCs, and upregulate Sox2 expression, which is targeted by miR34a [12].…”