Background:Circular RNAs(circRNAs)play a pivotal role in the development and advancement of various cancer types.However,the involvement of circ-PAN3 in hepatocellular carcinoma(HCC)is not well understood.To shed ligh...Background:Circular RNAs(circRNAs)play a pivotal role in the development and advancement of various cancer types.However,the involvement of circ-PAN3 in hepatocellular carcinoma(HCC)is not well understood.To shed light on this,we conducted a comprehensive study through biochemistry,cell biology,molecular biology,and bioinformatics techniques to investigate the role of circ-PAN3 and its associated pathway in the progression of HCC.Methods:Cell Counting Kit-8(CCK-8)assay and colony formation assay were utilized to evaluate cell proliferation;Quantitative real-time PCR(RT-qPCR)and Western blot were adopted for assessing mRNA and protein expression;Annexin V/propidium iodide(PI)staining was applied to detect cellular apoptosis;CircInteractome and Targetscan databases were searched to predict potential targets of circRNA and miRNA;Luciferase reporter assay and RNA pulldown assay were performed to examine the interaction of RNA molecules.Conclusions:Our findings revealed a significant increase in circ-PAN3 expression in HCC clinical specimens,which correlated with a poor survival rate in HCC patients.Knockdown of circ-PAN3 resulted in impaired cell proliferation,reduced cell survival,and inhibited tumorigenesis of HCC in vivo.Further analysis demonstrated that circ-PAN3 could serve as a sponge for miR-153,leading to a decrease in its expression level.This in turn upregulated cyclin D1 and ultimately promoted the proliferation of HCC cells.Additionally,overexpression of cyclin D1 mitigated the inhibitory effect on HCC proliferation induced by circ-PAN3 knockdown.Our study highlights the presence of a novel circ-PAN3/miR-153/cyclin D1 regulatory axis that plays a crucial role in the progression of HCC.展开更多
基金the National Natural Science Foundation of China(Grants No.81272659 to Renyin Qin,81602475 to Xingjun Guo,81502633 Xu Li)。
文摘Background:Circular RNAs(circRNAs)play a pivotal role in the development and advancement of various cancer types.However,the involvement of circ-PAN3 in hepatocellular carcinoma(HCC)is not well understood.To shed light on this,we conducted a comprehensive study through biochemistry,cell biology,molecular biology,and bioinformatics techniques to investigate the role of circ-PAN3 and its associated pathway in the progression of HCC.Methods:Cell Counting Kit-8(CCK-8)assay and colony formation assay were utilized to evaluate cell proliferation;Quantitative real-time PCR(RT-qPCR)and Western blot were adopted for assessing mRNA and protein expression;Annexin V/propidium iodide(PI)staining was applied to detect cellular apoptosis;CircInteractome and Targetscan databases were searched to predict potential targets of circRNA and miRNA;Luciferase reporter assay and RNA pulldown assay were performed to examine the interaction of RNA molecules.Conclusions:Our findings revealed a significant increase in circ-PAN3 expression in HCC clinical specimens,which correlated with a poor survival rate in HCC patients.Knockdown of circ-PAN3 resulted in impaired cell proliferation,reduced cell survival,and inhibited tumorigenesis of HCC in vivo.Further analysis demonstrated that circ-PAN3 could serve as a sponge for miR-153,leading to a decrease in its expression level.This in turn upregulated cyclin D1 and ultimately promoted the proliferation of HCC cells.Additionally,overexpression of cyclin D1 mitigated the inhibitory effect on HCC proliferation induced by circ-PAN3 knockdown.Our study highlights the presence of a novel circ-PAN3/miR-153/cyclin D1 regulatory axis that plays a crucial role in the progression of HCC.
