C1QTNF1-AS1 regulates the occurrence and development of hepatocellular carcinoma by regulating miR-221-3p/SOCS3
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The aim of our study was to explore how C1QTNF1-AS1 regulated miR-221-3p/SOCS3 axis in human hepatocellular carcinoma (HCC).
Differentially expressed lncRNAs and genes were examined via RNA-seq. GO analysis and KEGG pathway enrichment analysis were carried out based on the function of dys-regulated mRNAs. RT-qPCR was employed to detect the relative mRNA expression level of C1QTNF1-AS1, miR-221-3p, SOCS3 and key genes in the JAK/STAT signaling pathway in HCC tissues and cells, and western blot analysis was conducted to detect the relative protein expression levels of SOCS3 and key proteins in the JAK/STAT signaling pathway in HCC tissues and cells. MTT assay, transwell assay and flow cytometry were utilized to assess HCC cell proliferation, invasion, migration and apoptosis. Dual luciferase reporter gene assay was used to verify the targeted relationship between C1QTNF1-AS1 and miR-221-3p, as well as between miR-221-3p and SOCS3. A tumorigenicity assay in nude mice was conducted to investigate the effects of C1QTNF1-AS1 on HCC tumor growth in vivo.
C1QTNF1-AS1 and SOCS3 were down-regulated, while miR-221-3p was up-regulated in HCC tissues and cells. In HepG2 and Huh7 cells, overexpression of C1QTNF1-AS1 or SOCS3, as well as silence of miR-221-3p inhibited HCC cell proliferation, migration, and invasion and promoted HCC cell apoptosis. The results of the dual luciferase reporter gene assay indicated that miR-221-3p could directly target both C1QTNF1-AS1 and SOCS3. In addition, up-regulation of C1QTNF1-AS1 suppressed HCC tumor growth in vivo.
Overexpression of C1QTNF1-AS1 down-regulated miR-221-3p and subsequently up-regulated SOCS3, thereby inhibiting HCC cell proliferation, migration and invasion and promoting apoptosis through the JAK/STAT signaling pathway.
KeywordsC1QTNF1-AS1 miR-221-3p SOCS3 Hepatocellular carcinoma
Compliance with ethical standards
Conflict of interest
Hang Li, Bo Zhang, Meng Ding, Shang Lu, Hui Zhou, Dajun Sun, Gang Wu and Xianfeng Gan declare that they have no competing interests.
All procedures performed in studies involving animal participants were in accordance with the ethical standards of China-Japan Union Hospital, Jilin University. The entire study was approved by the China-Japan Union Hospital, Jilin University.
Informed consent was collected from patients to approve utilization of their tissues for research purposes.
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