Lanzhou University Second Hospital; Lanzhou University Second Clinical Medical College, China.
Department of General Surgery, Lanzhou University Second Hospital; Lanzhou University Second Clinical Medical College, Lanzhou, Gansu, China.
Biochem Cell Biol. 2021 Apr;99(2):249-260. doi: 10.1139/bcb-2020-0017. Epub 2020 Sep 27.
Colorectal cancer (CRC) is the third-most prevalent malignant tumor. Taurine upregulated gene 1 (TUG1), a long non-coding RNA (lncRNA), is reportedly involved in the physiological and pathological processes of CRC. However, the role of TUG1 in the progression of CRC and its underlying mechanisms are largely unknown. Here, we measured the expression of TUG1 in clinical samples from CRC patients and found that the expression level of TUG1 was higher in CRC tissues compared with the normal adjacent tissues. We then performed knockdown of TUG1 with siRNAs in two CRC cell lines and found that TUG1 knockdown inhibited the viability, proliferation, and migration of CRC cells, and reduced the ability of CRC cells to form subcutaneous tumors. Furthermore, we discovered that TUG1 affects the cellular processes in CRC cells by sponging miR-145-5p. We further found that miR-145-5p inhibits the expression of the protein-encoding gene (), and that overexpression of restored the inhibitory role of miR-145-5p in CRC cells. In conclusion, we have demonstrated that TUG1 exerts its role by modulating the TUG1-miR-145-5p-TRPC6 regulatory axis, thus revealing a novel molecular mechanism for the effects of TUG1 in the progression of CRC. Our data indicate that the TUG1-miR-145-5p-TRPC6 signaling pathway could serve as a target for the diagnosis and treatment of CRC.
结直肠癌(CRC)是第三大常见恶性肿瘤。牛磺酸上调基因 1(TUG1)是一种长链非编码 RNA(lncRNA),据报道参与了结直肠癌的生理和病理过程。然而,TUG1 在 CRC 进展中的作用及其潜在机制在很大程度上尚不清楚。在这里,我们测量了来自 CRC 患者的临床样本中的 TUG1 表达水平,发现 TUG1 的表达水平在 CRC 组织中高于正常相邻组织。然后,我们使用 siRNA 在两种 CRC 细胞系中敲低 TUG1,发现 TUG1 敲低抑制了 CRC 细胞的活力、增殖和迁移,并降低了 CRC 细胞形成皮下肿瘤的能力。此外,我们发现 TUG1 通过海绵 miR-145-5p 影响 CRC 细胞中的细胞过程。我们进一步发现 miR-145-5p 抑制了蛋白编码基因()的表达,而过表达 恢复了 miR-145-5p 在 CRC 细胞中的抑制作用。总之,我们已经证明 TUG1 通过调节 TUG1-miR-145-5p-TRPC6 调节轴发挥作用,从而揭示了 TUG1 在 CRC 进展中的作用的新分子机制。我们的数据表明,TUG1-miR-145-5p-TRPC6 信号通路可以作为 CRC 诊断和治疗的靶点。
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