biostudies-literatureChi BNatural Science Foundation of ChongqingScience and Health Research Project of ChongqingNational Natural Science Foundation of ChinaNatural Science Foundation of Yuzhong District of Chongqing415https://www.ebi.ac.uk/biostudies/studies/S-EPMC9764499biostudies-literatureUnknown22(1)<h4>Background</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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.<h4>Conclusion</h4>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.Cancer cell internationalIncreased 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.PMC9764499cstc2020jcyj-msxmX0707 and cstc2022ycjh-bgzxm013782072723202101602021MSXM344Zheng YYang JLi JChi BFu WCai LGuo SWang HXie FTang PGu JWang XYin JfalseIncreased 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.<h4>Background</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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.<h4>Conclusion</h4>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.2022-01-01T00:00:00Z2022 Dec2026-05-27T19:14:13.312Z2025-05-18T12:48:26.01ZS-EPMC97644993653980710.1186/s12935-022-02835-0