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长链非编码 RNA TUG1 通过 TUG1-miR-145-5p-TRPC6 通路促进结直肠癌细胞的生长和迁移。

The lncRNA TUG1 promotes cell growth and migration in colorectal cancer via the TUG1-miR-145-5p-TRPC6 pathway.

机构信息

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.

出版信息

Biochem Cell Biol. 2021 Apr;99(2):249-260. doi: 10.1139/bcb-2020-0017. Epub 2020 Sep 27.


DOI:10.1139/bcb-2020-0017
PMID:32985219
Abstract

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.

摘要

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。

相似文献

[1]
The lncRNA TUG1 promotes cell growth and migration in colorectal cancer via the TUG1-miR-145-5p-TRPC6 pathway.

Biochem Cell Biol. 2021-4

[2]
LncRNA TUG1 promotes the progression of colorectal cancer via the miR-138-5p/ZEB2 axis.

Biosci Rep. 2020-6-26

[3]
Long noncoding RNA TUG1 regulates the progression of colorectal cancer through miR-542-3p/TRIB2 axis and Wnt/β-catenin pathway.

Diagn Pathol. 2021-5-24

[4]
Insulin-like growth factor 2 mRNA-binding protein 2-stabilized long non-coding RNA Taurine up-regulated gene 1 (TUG1) promotes cisplatin-resistance of colorectal cancer via modulating autophagy.

Bioengineered. 2022-2

[5]
LncRNA FTX Promotes Colorectal Cancer Cells Migration and Invasion by miRNA-590-5p/RBPJ Axis.

Biochem Genet. 2021-4

[6]
Long noncoding RNA PRKCQ-AS1 promotes CRC cell proliferation and migration via modulating miR-1287-5p/YBX1 axis.

J Cell Biochem. 2020-10

[7]
LncRNA TUG1 promoted KIAA1199 expression via miR-600 to accelerate cell metastasis and epithelial-mesenchymal transition in colorectal cancer.

J Exp Clin Cancer Res. 2018-5-18

[8]
Long Noncoding RNA Taurine-Upregulated Gene 1 Promotes Cell Proliferation and Invasion in Gastric Cancer via Negatively Modulating miRNA-145-5p.

Oncol Res. 2017-5-24

[9]
Long Noncoding RNA Taurine-Upregulated Gene1 (TUG1) Promotes Tumor Growth and Metastasis Through TUG1/Mir-129-5p/Astrocyte-Elevated Gene-1 (AEG-1) Axis in Malignant Melanoma.

Med Sci Monit. 2018-3-15

[10]
Non-coding RNA MFI2-AS1 promotes colorectal cancer cell proliferation, migration and invasion through miR-574-5p/MYCBP axis.

Cell Prolif. 2019-5-16

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