Abstract
Long noncoding RNAs (lncRNAs) show emerging roles in colorectal cancer (CRC) development and are considered to be involved in the potential mechanism of tumor malignancy. While Sox2 overlapping transcript (SOX2OT) has been implicated in the progression of multiple cancers, its role in CRC remains to be explored. In this study, in situ hybridization (ISH) and qRT-PCR were performed to establish the functional relationships between SOX2OT and CRC deranged in CRC tissue and cells. Subsequently, SOX2OT shRNAs vectors were transfected into CRC cells to performed loss-of-function assays to detect the potential role of SOX2OT on proliferation and metastasis in vitro and vivo. The results showed SOX2OT was an oncogene that was up-regulated in human CRC tissues and cell lines. SOX2OT silencing suppressed cell proliferation, migration, and invasion in CRC cells in vitro, and inhibited tumorigenesis in the mouse xenografts. Bioinformatic predictive analysis coupled with the dual-luciferase reporter, RNA immunoprecipitation (RIP), and functional rescue assay elucidated the mechanistic network of the SOX2OT-miR-194-5p-SOX5 axis in CRC. Mechanistically, SOX2OT acted as a competing endogenous RNA (ceRNA) to upregulate SOX5 by sponging miR-194-5p. Downregulated SOX2OT boosted miR-194-5p expression, thus decreased the protein level of SOX5, which suppresses tumorgenesis of CRC.
Highlights
With the changes in diet structure and lifestyle, the incidence of colorectal cancer (CRC) increases globally and it has been gradually ranked the top three in morbidity worldwide[1,2] significant advances in treatment have been achieved with the advance of new chemotherapeutical and biological agents, treatment of CRC remains a therapeutic challenge and metastasis is still the dominating cause of failure[3]
SRY-box containing gene 2 (Sox2) overlapping transcript (SOX2OT) was visualized with an in situ hybridization (ISH) probe and it was found the expression of SOX2OT was highly expressed in low-grade and highgrade CRC tissues even displayed stage-dependent higher expression manner (Fig. 1B) and the quantitative reverse transcriptionpolymerase chain reaction (qRT-PCR) results further confirmed these results (Fig. 1C)
The results showed that SOX2OT expression was significantly increased in CRC cell lines cells compared with normal cell lines (Fig. 1D)
Summary
With the changes in diet structure and lifestyle, the incidence of colorectal cancer (CRC) increases globally and it has been gradually ranked the top three in morbidity worldwide[1,2] significant advances in treatment have been achieved with the advance of new chemotherapeutical and biological agents, treatment of CRC remains a therapeutic challenge and metastasis is still the dominating cause of failure[3]. The overall 5-year survival rate of CRC was less than 50% with local and distant metastasis[4]. Many studies have shown that noncoding RNA (ncRNA) are closely related to tumor oncogenesis. The abnormal expression of long noncoding RNA (lncRNA) and microRNA (miRNA) can be detected in almost all CRC tumor tissues[5,6] LncRNA and miRNA are closely related to the occurrence and development of tumor, and play a very important role of oncogene or tumor suppressor gene in the development of tumor by regulating tumor cell proliferation, invasion, apoptosis and drug resistance[7,8] A variety of lncRNAs are closely related to the occurrence and development of CRC; their function and mechanisms remain to be fully elucidated. SRY-box containing gene 2 (Sox2) is a Official journal of the Cell Death Differentiation Association
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