Upregulation of lncRNA Sox2ot indicates a poor prognosis for patients with hepatocellular carcinoma and promotes cell invasion

Abstract

Long non-coding RNA Sox2 overlapping transcript (lncRNA Sox2ot) expression has been demonstrated to be upregulated in a number of types of tumor, and may act as an oncogene. The present study aimed to evaluate the clinical role of lncRNA Sox2ot and its association with the epithelial-mesenchymal transition in hepatocellular carcinoma (HCC). Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was performed to determine the expression of lncRNA Sox2ot in 86 cases of HCC tissues and adjacent non-tumor tissues. Kaplan-Meier and log-rank test was used to analyze the association between lncRNA Sox2ot expression and disease-free (DFS) or overall (OS) survival time. In addition, the capacity of HCC cells with lncRNA Sox2ot knockdown for invasion was evaluated via transwell cell invasion assays. RT-qPCR and western blot analyses were also performed to determine the mRNA and protein expression of Twist1, E-cadherin and N-cadherin in the HCC cells. It was indicated that lncRNA Sox2ot expression levels were significantly higher in HCC tissues compared with adjacent non-tumor tissues. Increased expression levels of lncRNA Sox2ot were associated with the tumor size, the tumor number and vein invasion in patients with HCC. An association was observed between lncRNA Sox2ot and the DFS and OS of patients with HCC. Furthermore, it was determined that cell invasion was inhibited following the siRNA knockdown of lncRNA Sox2ot in MHCC97H and SMCC-7721 cells via transwell cell invasion assays. Furthermore, it was demonstrated that knockdown of lncRNA Sox2ot downregulated the mRNA and protein expression of Twist1 and N-cadherin, but upregulated the E-cadherin expression levels in MHCC97H and SMCC-7721 cells. Thus, it was indicated that lncRNA Sox2ot may be a novel predictive biomarker and a potential therapeutic target for HCC.

Clinicopathological Implication of Long Non-Coding RNAs SOX2 Overlapping Transcript and Its Potential Target Gene Network in Various Cancers

“…Several studies have indicated that high expression of SOX2-OT is significantly related with the prognosis and clinicopathological outcomes in cancers (Hou et al, 2014;Shi and Teng, 2015;Iranpour et al, 2016;Zhang et al, 2016;Zou et al, 2016;Wang et al, 2017a;Wang et al, 2017b;Han et al, 2018;Li et al, 2018a;Li et al, 2018b;Sun et al, 2018;Wei et al, 2018;Xie et al, 2018). The crucial role that SOX2-OT may play in the progression of many cancers had been further outlined in reviews (Shahryari et al, 2015;Castro-Oropeza et al, 2018).…”

“…A meta-analysis by Jing et al proposed that the overexpression of SOX2-OT indicated higher TNM stage and a worse OS in cancer patients, but failed to predict distant metastasis and lymph node metastasis in Chinese cancer patients (Jing et al, 2017). Moreover, other studies since 2014 have investigated the relationship between SOX2-OT and the prognosis of cancer patients (Hou et al, 2014;Shi and Teng, 2015;Iranpour et al, 2016;Zhang et al, 2016;Zou et al, 2016;Wang et al, 2017a;Wang et al, 2017b;Han et al, 2018;Li et al, 2018a;Li et al, 2018b;Sun et al, 2018;Wei et al, 2018;Xie et al, 2018). The present study was performed to obtain a more definite conclusion and assess the potential mechanisms of SOX2-OT effects by integrating the outcomes of published studies and TCGA survival data and running GO and KEGG analyses.…”

“…Eight studies that used multivariate analysis of OS were included in the meta-analysis (Hou et al, 2014;Shi and Teng, 2015;Zhang et al, 2016;Zou et al, 2016;Wang et al, 2017a;Li et al, 2018a;Li et al, 2018b;Xie et al, 2018), the adjusted variables of the multivariate analysis were presented in Table 2. The other three studies provided survival curves (Zhang et al, 2017;Sun et al, 2018;Wei et al, 2018).…”

“…It has been shown that lncRNA SOX2-OT is overexpressed in a number of human cancers as an oncogene promoting tumorigenesis and cancer progression, including ovarian cancer, breast cancer, pancreatic ductal adenocarcinoma, cholangiocarcinoma, hepatocellular carcinoma, esophageal squamous cell carcinoma, osteosarcoma, non-small cell lung cancer, and gastric cancer (Iranpour et al, 2016;Zhang et al, 2016;Zou et al, 2016;Wang et al, 2017a;Wang et al, 2017b;Han et al, 2018;Li et al, 2018a;Li et al, 2018b;Sun et al, 2018;Tian et al, 2018;Wei et al, 2018;Xie et al, 2018). SOX2-OT is co-upregulated with SOX2 and OCT4 in esophageal squamous cell carcinoma and potentially involved in maintaining the pluripotent state of stem cells (Shahryari et al, 2014).…”

“…Although these articles established the critical role of lncRNA SOX2-OT expression in some cancers, the prognostic value of SOX2-OT expression in numerous other cancers remained uncharacterized (Shahryari et al, 2015;Castro-Oropeza et al, 2018;Farhangian et al, 2018). In addition, inconsistent results were obtained in several studies on the association between SOX2-OT expression and clinical features such as tumor size, clinical stage, and tumor invasion (Shi and Teng, 2015;Zou et al, 2016;Wang et al, 2017a;Li et al, 2018b;Sun et al, 2018).…”