Increased expression of miR-194-5p through the circPVRL3/miR-194-5p/SOCS2 axis promotes proliferation and metastasis in pancreatic ductal adenocarcinoma by activating the PI3K/AKT signaling pathway

作者全名："Chi, Bojing; Zheng, Yao; Xie, Fuming; Fu, Wen; Wang, Xianxing; Gu, Jianyou; Yang, Jiali; Yin, Jingyang; Cai, Lei; Tang, Peng; Li, Jianbo; Guo, Shixiang; Wang, Huaizhi"

作者地址："[Chi, Bojing] Univ Chinese Acad Sci, Savaid Med Sch, Beijing 100049, Peoples R China; [Chi, Bojing; Zheng, Yao; Xie, Fuming; Fu, Wen; Wang, Xianxing; Gu, Jianyou; Yang, Jiali; Yin, Jingyang; Cai, Lei; Tang, Peng; Li, Jianbo; Guo, Shixiang; Wang, Huaizhi] Chongqing Gen Hosp, Inst Hepatopancreatobiliary Surg, Chongqing 401147, Peoples R China; [Zheng, Yao; Wang, Xianxing; Yang, Jiali; Guo, Shixiang; Wang, Huaizhi] Chongqing Key Lab Intelligent Med Engn Hepatopancr, Chongqing 401147, Peoples R China; [Xie, Fuming; Fu, Wen; Yin, Jingyang] Chongqing Med Univ, Chongqing 400016, Peoples R China; [Wang, Huaizhi] Univ Chinese Acad Sci, Coll Life Sci, Beijing 100049, Peoples R China"

通信作者："Li, JB; Guo, SX; Wang, HZ (通讯作者)，Chongqing Gen Hosp, Inst Hepatopancreatobiliary Surg, Chongqing 401147, Peoples R China.; Guo, SX; Wang, HZ (通讯作者)，Chongqing Key Lab Intelligent Med Engn Hepatopancr, Chongqing 401147, Peoples R China.; Wang, HZ (通讯作者)，Univ Chinese Acad Sci, Coll Life Sci, Beijing 100049, Peoples R China."

来源：CANCER CELL INTERNATIONAL

ESI学科分类：MOLECULAR BIOLOGY & GENETICS

WOS号：WOS:000901787300001

JCR分区：Q1

影响因子：5.8

年份：2022

卷号：22

期号：1

开始页：　

结束页：　

文献类型：Article

关键词：Circular RNA; miR-194-5p; Cell cycle; Pancreatic ductal adenocarcinoma

摘要："Background: MicroRNAs (miRNAs), as an indispensable type of non-coding RNA (ncRNA), participate in diverse biological processes. However, the specific regulatory mechanism of certain miRNAs in pancreatic ductal adenocarcinoma (PDAC) remains unclear. Methods: The expression of miR-194-5p in PDAC tissue microarray and cell lines were detected by RNA-scope and real-time quantitative PCR (RT-qPCR). The function of proliferation and migration carried by miR-194-5p in vitro and vivo was observed by several functional experiments. Informatics methods and RNA sequencing data were applied to explore the target of miR-194-5p and the upstream circular RNA (circRNA) of miR-194-5p. RNA-binding protein immunoprecipitation (RIP) assay and dual-luciferase reporter assay confirmed the relationships between miR-194-5p and SOCS2 or miR-194-5p and circPVRL3. The proliferation and migration abilities of SOCS2 and circPVRL3 were accessed by rescue experiments. Results: In this study, we aimed to clarify the molecular mechanisms of miR-194-5p, which has critical roles during PDAC progression. We found that the expression of miR-194-5p was significantly upregulated in PDAC tissue compared to tumor-adjacent tissue and was highly related to age and nerve invasion according to RNAscope and RT-qPCR. Overexpression of miR-194-5p accelerated the cell cycle and enhanced the proliferation and migration processes according to several functional experiments in vitro and in vivo. Specifically, circPVRL3, miR-194-5p, and SOCS2 were confirmed to work as competing endogenous RNAs (ceRNAs) according to informatics methods, RIP, and dual-luciferase reporter assays. Additionally, the rescue experiments confirmed the relationship among miR-194-5p, circPVRL3, and SOCS2 mRNA. Finally, the circPVRL3/miR-194-5p/SOCS2 axis activates the PI3K/AKT signaling pathway to regulate the proliferation and metastasis of PDAC. Conclusion: Our findings indicated that an increase of miR-194-5p caused by circPVRL3 downregulation stimulates the PI3K/AKT signaling pathway to promote PDAC progression via the circPVRL3/miR-194-5p/SOCS2 axis, which suggests that the circPVRL3/miR-194-5p/SOCS2 axis may be a potential therapeutic target for PDAC patients."

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