hsa_circRNA_002144 通过调控 miR-615-5p/LARP1/mTOR 通路促进结直肠癌细胞的生长和转移。
Hsa_circRNA_002144 promotes growth and metastasis of colorectal cancer through regulating miR-615-5p/LARP1/mTOR pathway.
机构信息
Department of Gynecology Xiuying District, Haikou City, Hainan Province, China.
Department of Endoscopy Center Xiuying District, Haikou City, Hainan Province, China.
出版信息
Carcinogenesis. 2021 Apr 30;42(4):601-610. doi: 10.1093/carcin/bgaa140.
CircRNAs (circular RNAs), recently identified as a critical regulator in tumorigenesis, participate in CRC (colorectal cancer) growth. However, the role of hsa_circRNA_002144 in CRC was poorly understood. Firstly, hsa_circRNA_002144 showed significantly elevation in both of CRC tissues and cell lines, and suggested closely associated with poor prognosis in patients. Secondly, data from functional assays revealed that silence of hsa_circRNA_002144 inhibited CRC progression with reduced cell viability, proliferation, migration and invasion, while enhanced cell apoptosis. In addition, in vivo CRC growth and metastasis were also suppressed by knockdown of hsa_circRNA_002144. However, CRC progression was promoted with over-expression of hsa_circRNA_002144. Thirdly, hsa_circRNA_002144 colocalized with miR-615-5p in the cytoplasm of CRC cells, and decreased miR-615-5p expression. Moreover, miR-615-5p could target LARP1 (La ribonucleoprotein 1, translational regulator). Lastly, the suppressive effects of hsa_circRNA_002144 knockdown on CRC progression were reversed by LARP1 over-expression. In conclusion, hsa_circRNA_002144 could sponge miR-615-5p to promote CRC progression through the regulation of LARP1, providing a therapeutic target for cancer intervention.
CircRNAs（环状 RNA），最近被鉴定为肿瘤发生中的关键调节因子，参与 CRC（结直肠癌）的生长。然而，hsa_circRNA_002144 在 CRC 中的作用知之甚少。首先，hsa_circRNA_002144 在 CRC 组织和细胞系中均显著升高，并提示与患者预后不良密切相关。其次，功能测定数据表明，沉默 hsa_circRNA_002144 可抑制 CRC 进展，降低细胞活力、增殖、迁移和侵袭，同时促进细胞凋亡。此外，敲低 hsa_circRNA_002144 还抑制了体内 CRC 的生长和转移。然而，hsa_circRNA_002144 的过表达促进了 CRC 的进展。第三，hsa_circRNA_002144 与 CRC 细胞细胞质中的 miR-615-5p 共定位，并降低了 miR-615-5p 的表达。此外，miR-615-5p 可以靶向 LARP1（La 核糖核蛋白 1，翻译调节剂）。最后，hsa_circRNA_002144 敲低对 CRC 进展的抑制作用被 LARP1 的过表达逆转。总之，hsa_circRNA_002144 可以通过海绵吸附 miR-615-5p 来促进 CRC 的进展，通过调节 LARP1 提供癌症干预的治疗靶点。
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