TNNT1, negatively regulated by miR-873, promotes the progression of colorectal cancer.

ABSTRACT

BACKGROUND: Troponin T1 (TNNT1) is a subunit of troponin that has been linked to neuromuscular disorder. Recently, it was reported that TNNT1 facilitates the proliferation of breast cancer cells. Interestingly, Cancer Genome Atlas data indicate that its overexpression is associated with an unfavorable prognosis of colorectal cancer (CRC) patients. The present study aimed to explore the expression, function and mechanism of dysregulation of TNNT1 in CRC. METHODS: Immunohistochemical staining and a real-time polymerase chain reaction were used to compare the expression level of TNNT1 in CRC tissues and adjacent tissues. Western blotting was used to detect the expression of TNNT1 in cell lines. Kaplan-Meier analysis and a chi-squared test were applied to evaluate the potential of TNNT1 to function as a cancer biomarker. RNA interference was used to inhibit TNNT1 expression in CRC cells, followed by detection of cell proliferation, apoptosis, migration and invasion. A luciferase reporter gene assay was used to determine the regulatory relationship between miR-873 and TNNT1. RESULTS: In the present study, we found that TNNT1 was significantly up-regulated in CRC samples and cell lines. The up-regulation of TNNT1 was also associated with several clinicopathologic features, and its high expression was correlated with an unfavorable prognosis of the patients. Knockdown of TNNT1 markedly arrested proliferation, migration and invasion, whereas it also promoted apoptosis. TNNT1 was identified as a target gene of miR-873, and there was a negative correlation among CRC samples. CONCLUSIONS: In conclusion, we have demonstrated that TNNT1, regulated by miR-873, is an oncogene of CRC associated with patient prognosis.