摘要
环状RNA(circular RNAs,circRNAs)是一类新型的长非编码RNA,已有研究表明circRNAs可调控肿瘤的发生发展。本研究首先通过高通量测序技术检测5对结直肠癌组织及其配对的癌旁正常组织中的circRNAs差异表达谱,鉴定出477种差异表达的circRNAs,其中252种表达上调,225种表达下调,选取表达上调最为显著的circRNA——circPVT1(circRNA plasmacytoma variant translocation 1,circPVT1),利用实时荧光定量PCR(qRT-PCR)检测150对结直肠癌组织及癌旁正常组织样本中circPVT1的表达水平,获得与高通量测序一致性结果,进一步证实circPVT1在结直肠癌中高表达。同时,在多种结直肠癌细胞系中证实circPVT1的表达较正常结直肠黏膜细胞高,差异均具有统计学意义(P<0.05)。在功能上,通过在结直肠癌细胞中沉默或过表达circPVT1,分析其对细胞增殖、凋亡及细胞周期的影响,借以阐明circPVT1在结直肠癌中的生物学功能。结果表明,circPVT1在体外可显著抑制结直肠癌细胞的凋亡、加快细胞周期进程以促进结直肠癌细胞增殖。综上所述,circPVT1在结直肠癌的生长过程中发挥促癌作用,有望作为治疗结直肠癌的潜在靶点。
Circular RNAs(circRNAs)are a novel class of long-chain non-coding RNAs.Preceding evidence has showed that circRNAs participate in the development and progression of various tumors.In the present study,we investigated the expression of circRNAs in 5 paired colorectal cancer(CRC)tissues and adjacent normal tissues with circRNA high-throughput sequencing.Totally 477 differentially expressed circRNAs were identified between CRC tissues and non-cancerous matched tissues,which included 252 significantly overexpressed circRNAs and 225 downregulated circRNAs.CircRNA plasmacytoma variant translocation 1(circPVT1),the most up-regulated expression circRNA,was further confirmed by qRT-PCR in 150 colorectal cancer tissues and matched normal mucosae.Our data revealed that circPVT1 showed a significant up-regulation trend in CRC tissues compared with matched normal mucosae.Similarly,compared with normal colorectal mucosa cells,the expression of circPVT1 in colorectal cancer cell lines was significantly up-regulated(P<0.05).Functionally,silence with siRNA or overexpression of circPVT1 in colorectal cancer cells was applied to determine the biological functions of circPVT1,including cell proliferation,apoptosis,and cell cycle,etc.The results show that circPVT1 expression significantly attenuated apoptosis,induced replication and promoted proliferation of colorectal cancer cells in vitro.In summary,our findings indicate that circPVT1 plays an oncogenic role in CRC and might be a potential novel target for CRC therapy.
作者
李韵
金子慧
张瑞瑞
楼哲丰
金红蕾
LI Yun;JIN Zi-Hui;ZHANG Rui-Rui;LOU Zhe-Feng;JIN Hong-Lei(School of Laboratory Medicine and Life Sciences,Wenzhou Medical University,Wenzhou 325035,Zhejiang,China)
出处
《中国生物化学与分子生物学报》
CAS
CSCD
北大核心
2021年第9期1241-1249,共9页
Chinese Journal of Biochemistry and Molecular Biology
基金
温州市科技局(No.Y20190065)
国家级大学生创新创业训练计划项目(No.201910343030)资助。
关键词
结直肠癌
circPVT1
增殖
凋亡
colorectal cancer(CRC)
circular RNA PVT1(circPVT1)
proliferation
apoptosis
