INTS6 (integrator complex subunit 6) has been reported as a tumor suppressor in many cancers. However, the expression and biological function of INTS6 in colorectal cancer (CRC) has not been investigated yet. In this study, we found that INTS6 expression was significantly increased in CRC tissues when compared with normal tissues and was associated with poor prognosis. Downregulation of INTS6 induced G1/S-phase cell cycle arrest, and markedly suppressed the growth of CRC cells and the derived tumors, while overexpression of INTS6 showed opposite effect. Mechanism study revealed that INTS6 increased the levels of phosphorylated AKT (p-AKT) and ERK (p-ERK), and the growth-promoting effect of INTS6 was inhibited by AKT and ERK inhibitors. Besides, INTS6 also affected the expression of two targets of PI3K/AKT and MAPK signaling, c-Myc and CDK2, which contributed to cell cycle alteration. Altogether, the present study has revealed the oncogenic role of INTS6 in CRC, providing a novel therapeutic target for this malignant cancer.

INTS6（整合子复合物亚基 6）已被报道为许多癌症中的肿瘤抑制因子。然而，INTS6 在结直肠癌 (CRC) 中的表达和生物学功能尚未得到研究。在这项研究中，我们发现与正常组织相比，结直肠癌组织中的 INTS6 表达显着增加，并且与预后不良有关。INTS6 的下调诱导 G1/S 期细胞周期停滞，并显着抑制 CRC 细胞和衍生肿瘤的生长，而 INTS6 的过表达则显示出相反的效果。机制研究表明，INTS6提高了磷酸化AKT（p-AKT）和ERK（p-ERK）的水平，并且INTS6的促生长作用被AKT和ERK抑制剂抑制。此外，INTS6 还影响 PI3K/AKT 和 MAPK 信号传导的两个靶标 c-Myc 和 CDK2 的表达，这有助于细胞周期的改变。总之，本研究揭示了 INTS6 在 CRC 中的致癌作用，为这种恶性癌症提供了一个新的治疗靶点。