The promoting effects of hsa_circ_0050102 in pancreatic cancer and the molecular mechanism by targeting miR-1182/NPSR1
The promoting effects of hsa_circ_0050102 in pancreatic cancer and the molecular mechanism by targeting miR-1182/NPSR1
复制标题
hsa_circ_0050102对胰腺癌的促进作用及靶向miR-1182/NPSR1的分子机制
DOI：
10.1093/carcin/bgaa130
复制
发表时间：
2021-01-09
期刊：
影响因子：
4.7
通讯作者：
Liao, Quan
中科院分区：
文献类型：
--
作者：
Hua, Surong;Gao, Junyi;Liao, Quan
胰腺癌是世界上致死率最高的肿瘤之一，总的5年生存率为9%，在过去的几十年里，人们一直致力于早期诊断和治疗。竞争性内源RNA是一种新的特异性基因表达调控机制，研究表明其在肿瘤调控中具有重要作用。本研究探讨circ-0050102在胰腺癌中的表达及其对肿瘤恶性表型的影响，并进一步研究circ-0050102、miR-1182和NPSR 1之间的相关性。实时荧光定量PCR结果显示circ-0050102在胰腺癌组织中的表达高于癌旁正常组织。在细胞功能实验中，circ-0050102的下调可以抑制PANC-1和CFPAC-1细胞的细胞增殖、迁移和侵袭能力，促进细胞凋亡并阻滞细胞周期。此外，进行了裸鼠同种异体移植，结果表明circ-0050102的抑制可以减缓体内肿瘤形成。机制研究表明，circ-0050102可下调miR-1182的表达，而miR-1182对circ-0050102的表达无影响，miR-1182可直接靶向NPSR 1并抑制其表达，circ-0050102可逆转si-NPSR 1对胰腺癌细胞的作用。总之，我们确定circ-0050102通过调节miR-1182/NPSR 1通路在促进胰腺癌中发挥重要作用。
Pancreatic cancer is one of the most lethal tumors across the world with an overall 5-year survival rate of 9%, and great efforts have been devoted in early diagnosis and treatment in the past decades. Competing endogenous RNAs are novel and specific regulatory mechanisms of gene expression, and researches have indicated its important roles in tumor regulation. In this study, we explored the circ-0050102 expression in pancreatic cancer and its impacts on tumor malignant phenotypes and further investigated the correlations among circ-0050102, miR-1182 and NPSR1. Results of real-time quantitative PCR showed that circ-0050102 expressed higher in pancreatic cancers compared with that in adjacent normal tissues. In cell functional experiment, downregulation of circ-0050102 could suppress cell proliferation, migration and invasion ability, boost cell apoptosis and arrest cell cycle in both PANC-1 and CFPAC-1 cells. Furthermore, allogeneic transplantation in nude mice was performed and results showed that the inhibition of circ-0050102 could slow down tumor formation in vivo. Mechanism research suggested that circ-0050102 could downregulate miR-1182, while miR-1182 could not influence the expression of circ-0050102, and miR-1182 could directly target at NPSR1 and suppress it. Moreover, circ-0050102 could reverse the effects of si-NPSR1 on pancreatic cancer cells. In conclusion, we identified that circ-0050102 played an important role in promoting pancreatic cancer by regulating the miR-1182/NPSR1 pathway.