Yang Jinghui, Cong Xianling, Ren Ming, Sun Hongyan, Liu Tao, Chen Gaoyang, Wang Qingyu, Li Zhaoyan, Yu Shan, Yang Qiwei
Department of Hepatopancreatobiliary Surgery, China-Japan Union Hospital of Jilin University, Changchun 130033, China.
Tissue Bank, China-Japan Union Hospital of Jilin University, Changchun 130033, China.
J Oncol. 2019 Jul 24;2019:7630894. doi: 10.1155/2019/7630894. eCollection 2019.
Pancreatic cancer remains one of the leading causes of cancer-related deaths worldwide. Pancreatic ductal adenocarcinoma (PDAC) is the most common type of pancreatic tumor. Many circular RNAs (circRNAs) have proven to play vital roles in the physiological and pathological processes of tumorigenesis; however, their biogenesis in PDAC remains unclear. In this study, the expression profiles of circRNAs from 10 PDAC tissues and their paired adjacent nontumor tissues were analyzed through RNA sequencing analysis. An enrichment analysis was employed to predict the functions of the differentially expressed circRNAs. Sequence alignment information and mRNA microarray projects were used to predict the RNA regulatory network. The knockdown of circRNAs by small interfering RNAs followed by wound healing and western blot assays was used to confirm their functions in a PDAC cell line. A total of 278 circRNAs were identified as differentially expressed in PDAC tissue. Of these, we found that hsa_circRNA_0007334 was significantly upregulated and may serve as a competing endogenous RNA to regulate matrix metallopeptidase 7 (MMP7) and collagen type I alpha 1 chain (COL1A1) by the competitive adsorption of hsa-miR-144-3p and hsa-miR-577 to enhance the expression and functions of MMP7 and COL1A1 in PDAC. In vitro experiments confirmed these results. The present study is the first to propose two regulatory pathways in PDAC: hsa_circRNA_0007334-hsa-miR-144-3p-MMP7 and hsa_circRNA_0007334-hsa-miR-577-COL1A1.
胰腺癌仍然是全球癌症相关死亡的主要原因之一。胰腺导管腺癌(PDAC)是最常见的胰腺肿瘤类型。许多环状RNA(circRNA)已被证明在肿瘤发生的生理和病理过程中发挥重要作用;然而,它们在PDAC中的生物发生仍不清楚。在本研究中,通过RNA测序分析了10个PDAC组织及其配对的相邻非肿瘤组织中circRNA的表达谱。采用富集分析来预测差异表达circRNA的功能。利用序列比对信息和mRNA微阵列项目来预测RNA调控网络。通过小干扰RNA敲低circRNA,随后进行伤口愈合和蛋白质印迹分析,以确认它们在PDAC细胞系中的功能。共鉴定出278个在PDAC组织中差异表达的circRNA。其中,我们发现hsa_circRNA_0007334显著上调,并可能作为一种竞争性内源RNA,通过竞争性吸附hsa-miR-144-3p和hsa-miR-577来调节基质金属肽酶7(MMP7)和I型胶原α1链(COL1A1),从而增强MMP7和COL1A1在PDAC中的表达和功能。体外实验证实了这些结果。本研究首次提出了PDAC中的两条调控途径:hsa_circRNA_0007334-hsa-miR-144-3p-MMP7和hsa_circRNA_0007334-hsa-miR-577-COL1A