CircC16orf62 promotes hepatocellular carcinoma progression through the miR-138-5p/PTK2/AKT axis.
CircC16orf62 promotes hepatocellular carcinoma progression through the miR-138-5p/PTK2/AKT axis.
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CircC16orf62通过miR-138-5p/PTK2/AKT轴促进肝细胞癌进展
DOI：
10.1038/s41419-021-03866-7
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发表时间：
2021-06-09
影响因子：
9
通讯作者：
Zhou S
中科院分区：
文献类型：
--
作者：
Zhang S;Lu Y;Jiang HY;Cheng ZM;Wei ZJ;Wei YH;Liu T;Xia BJ;Zhao XY;Huang Y;Zou X;Liu R;Zhou S
环状RNA（circRNA）在肝细胞癌（HCC）的发病和进展中起着至关重要的作用。然而，某些circRNA的表达和功能对肿瘤的转移和增殖仍不清楚。生物信息学分析和qRT-PCR结果表明，CircC 16 orf 62在HCC中显著上调，其表达水平与癌症的恶性进展呈正相关。功能获得或丧失研究表明，CircC 16 orf 62表达的减少促进了体外和体内HCC的增殖、侵袭和糖酵解。生物信息学分析发现miR-138- 5 p和PTK 2是CircC 16或62的下游靶点。荧光免疫原位杂交（FISH）和细胞核质分离证实CircC 16 orf 62定位于细胞质中。使用质粒载体或siRNA来改变PC细胞系中CircC 16 orf 62、miR-138- 5 p和PTK 2的表达。CircC 16 orf 62作为miR-138- 5 p的分子海绵和PTK 2的竞争性内源性RNA发挥作用，促进AKT/mTOR通路活化。我们的观察使我们得出结论，CircC 16 orf 62在HCC进展中作为癌基因发挥作用，表现为miR-138- 5 p结合的竞争性内源性RNA，从而激活AKT/mTOR通路。综上所述，CircC 16 orf 62是HCC细胞中通过miR-138- 5 p/PTK 2/Akt轴的癌基因，表明CircC 16 orf 62可以是具有潜力的肝癌治疗靶点和HCC患者的预测标志物。
Circular RNA (circRNAs) functions vital in the pathogenesis and progression of hepatocellular carcinoma (HCC). However, the expressions and functions of certain circRNAs on metastasis and proliferation of that cancer is still unclear. Bioinformation analysis and qRT-PCR indicated that CircC16orf62 was prominent upregulated in HCC of which the expression level was positively associated to cancer’s malignant progression. Gain or loss-of-function studies indicated that the reduction of CircC16orf62 expression promotes the proliferation, invasion, and glycolysis of HCC in vitro and in vivo. The bioinformatic analysis found that miR-138-5p and PTK2 were the downstream target of CircC16or62. Then, the FISH(Fluorescence immunoin situ hybridization) and cell nucleoplasmic separation determined that CircC16orf62 located in the cell cytoplasm. Plasmid vectors or siRNAs were used to change the expression of CircC16orf62, miR-138-5p, and PTK2 in PC cell lines. CircC16orf62 functioned as a molecular sponge for miR-138-5p, and a competitive endogenous RNA for PTK2, promoting AKT/mTOR pathway activation. Our observations lead us to conclude that CircC16orf62 functions as an oncogene in HCC progression, behaving as a competitive endogenous RNA for miR-138-5p binding, thus activating the AKT/mTOR pathway. In conclusion, CircC16orf62 is an oncogene through the miR-138-5p/PTK2/Akt axis in HCC cells, indicating CircC16orf62 can be a therapeutic target with potentiality for liver cancer and a predictive marker for people with HCC.
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