Tim-3 is upregulated in human colorectal carcinoma and associated with tumor progression

Abstract

T cell immunoglobulin mucin-3 (Tim-3) has previously been implicated in the immune response and tumor biology. Colorectal carcinoma (CRC) is a malignancy, which is closely associated with inflammation. However, the role of Tim-3 in the progression of CRC remains to be fully elucidated. The present study aimed to investigate the role of Tim-3 in the progressive activities of human CRC. A total of 30 clinical CRC tissues and their adjacent tissues were collected. Slides from another 112 cases that underwent CRC surgical resection were also obtained. The protein and mRNA levels of Tim-3 in the clinical tissues and in CRC cell lines were initially examined using western blot and reverse transcription-quantitative polymerase chain reaction analyses, respectively. Immunohistochemical staining was performed to detect Tim-3 in the CRC samples. Specific small interfering (si)RNA against Tim-3 (siTim-3) was synthesized to knock down the expression of Tim-3, and the subsequent effects of Tim-3 knockdown on cell proliferation, migration and invasion were assessed. The data obtained showed that Tim-3 was expressed at high levels in the CRC tissues, compared with the non-cancerous tissues. The expression of Tim-3 in the clinical tissues was significantly associated with tumor size (P=0.007), tumor-node-metastasis staging (P<0.0001) and distant metastasis (P<0.0001). Knockdown of Tim-3 significantly reduced the cell proliferative rate of HCT116 and HT-29 cells. Wound closure activity was also inhibited by knockdown of Tim-3 in these two cell lines, and the migration and invasive abilities of these two cell lines were consistently decreased following knockdown of Tim-3. Taken together, Tim-3 was found to be a critical mediator in the progression of CRC and may serve as a potential therapeutic target for the treatment of CRC.