ABSTRACT
An increasing number of studies have revealed the role of long non-coding RNAs in cancer. However, the mechanisms of action and functional utility in colorectal cancer (CRC) have not been fully elucidated. Here we describe the functional role and potential mechanism of TINCR (terminal differentiation-induced non-coding RNA) in CRC. Firstly, TINCR was selected using sequencing analyses and the starBase database. Cell Counting Kit-8, scratch wound healing, and transwell assays revealed that TINCR inhibited proliferation and migration in SW620 and HTC116 cells. Intriguingly, TINCR expression was up-regulated in a radioresistant CRC cell line (SW620R). Although TINCR had no significant effects on SW620R cell proliferation or migration, knockdown of TINCR reduced the radioresistance, and its overexpression had opposite effects. We then focused on transcription factor 4 (TCF4) as it is downregulated in CRC and associated with increased stemness in tumors. We found that TINCR and TCF4 levels were positively related in SW620R cells. TINCR knockdown reduced sphere formation ability in SW620R cells. TINCR also suppressed the OCT4 and SOX2 stemness genes, despite having no effect on NANOG. The expression levels of these genes were substantially higher in SW620R than in SW620 cells. To further explore the mechanism of TINCR and radioresistance, miR-137 was analyzed as it targets TCF4. We firstly confirmed that TCF4 is a target of miR-137. We then identified that TINCR knockdown enhanced miR-137 expression in SW620R cells. Collectively, these findings suggest that TINCR knockdown inhibits TCF4 by regulating miR-137 expression.
Subject(s)
Colorectal Neoplasms/pathology , Gene Expression Regulation, Neoplastic/genetics , MicroRNAs/genetics , RNA, Long Noncoding/genetics , Radiation Tolerance/genetics , Cell Line, Tumor , Gene Knockdown Techniques , Humans , Transcription Factor 4/biosynthesis , Transcription Factor 4/geneticsABSTRACT
Objective To investigate the prognostic value of neutrophil changes in patients with colorectal cancer.Methods The neutrophils in patients with colorectal cancer were classified into twotypes:peripheral blood neutrophils and tumor-associated neutrophils (TANs).Peripheral blood neutrophils are expressed as neutrophil/lymphocyte ratio (neutrophil to lymphocyte ratio,NLR).Results The 5 year's survival rates of patients with high and low NLR were 75.2％ and 88.2％,respectively.The 5 year's survival rates of patients with high and low TANs were 97.6％ and 64.2％,respectively.The survival rates of patients with low NLR and high TANs;high NLR and high infiltrating TANs;low NLR and low infiltrating TANs;and high NLR and low infiltrating TANs were respectively 100％,95.7％,76.4％ and 53.5％.With the two joining together the ability to distinguish long-term prognosis of patients was significantly better than any one alone.Multivariate regression analysis showed that,high peripheral blood NLR,low TANs infiltration,tumor located in the rectum,TNM staging are independent risk factors for colorectal cancer prognosis.Conclusions NLR in preoperative peripheral blood combined with infiltrating TANs in colorectal cancer tissues can be used as a prognostic indicator for patients with colorectal cancer.High NLR in preoperative peripheral blood combined with low infiltrating TANs in colorectal cancer tissue predicts poor prognosis.
