Background and Aims:General transcription factor IIIC subunit 2(GTF3C2)is one of the polymerase III transcription-related factors.Previous studies have revealed that GTF3C2 is involved in regulating cell proliferation...Background and Aims:General transcription factor IIIC subunit 2(GTF3C2)is one of the polymerase III transcription-related factors.Previous studies have revealed that GTF3C2 is involved in regulating cell proliferation.However,the role of GTF3C2 in hepatocellular carcinoma(HCC)remains un-clear.This study aimed to determine its expression,biologi-cal function,and mechanism in HCC.Methods:The expres-sion of GTF3C2 in HCC and non-tumor tissues,along with its clinical significance,was investigated using public databases and clinical samples.Reverse transcription-quantitative poly-merase chain reaction and Western blot assays were per-formed to detect the expression of GTF3C2,ubiquitin specific peptidase 21(USP21),mitogen-activated protein kinase 2(MEK2),extracellular signal-regulated kinase 1/2(ERK1/2),and p-ERK1/2 in cells.A luciferase reporter assay was con-ducted to explore the regulatory effect of GTF3C2 on USP21 transcription.Cell Counting Kit-8,5-ethynyl-2′-deoxyuridine,and colony formation assays were performed to assess HCC cell proliferation.Subcutaneous injection of HCC cells into nude mice was used to evaluate tumor growth in vivo.Re-sults:GTF3C2 expression was upregulated in HCC tissues and was positively correlated with advanced tumor stages and high tumor grades.HCC patients with high GTF3C2 ex-pression had significantly worse survival outcomes.Knock-down of GTF3C2 suppressed the proliferation of Hep3B and HCCLM3 cells,while overexpression of GTF3C2 facilitated the proliferation of SNU449 and Huh7 cells.GTF3C2 promoted USP21 expression by activating its transcription,which sub-sequently increased the levels of MEK2 and p-ERK1/2 in HCC cells.Overexpression of both USP21 and MEK2 counteracted the GTF3C2 knockdown-induced inactivation of the ERK1/2 pathway.Moreover,GTF3C2 promoted HCC cell proliferation in vitro and tumor growth in vivo by regulating the USP21/MEK2/ERK1/2 pathway.Conclusions:Upregulation of GT-F3C2 is frequently observed in HCC tissues and predicts poor prognosis.GTF3C2 promotes HCC cell proliferation via the USP21/MEK2/ERK1/2 pathway.展开更多
基金supported by a grant from the Huadong Medicine Joint Funds of the Zhejiang Provincial Natural Science Foundation of China(Grant No.LHDMD23H300002).
文摘Background and Aims:General transcription factor IIIC subunit 2(GTF3C2)is one of the polymerase III transcription-related factors.Previous studies have revealed that GTF3C2 is involved in regulating cell proliferation.However,the role of GTF3C2 in hepatocellular carcinoma(HCC)remains un-clear.This study aimed to determine its expression,biologi-cal function,and mechanism in HCC.Methods:The expres-sion of GTF3C2 in HCC and non-tumor tissues,along with its clinical significance,was investigated using public databases and clinical samples.Reverse transcription-quantitative poly-merase chain reaction and Western blot assays were per-formed to detect the expression of GTF3C2,ubiquitin specific peptidase 21(USP21),mitogen-activated protein kinase 2(MEK2),extracellular signal-regulated kinase 1/2(ERK1/2),and p-ERK1/2 in cells.A luciferase reporter assay was con-ducted to explore the regulatory effect of GTF3C2 on USP21 transcription.Cell Counting Kit-8,5-ethynyl-2′-deoxyuridine,and colony formation assays were performed to assess HCC cell proliferation.Subcutaneous injection of HCC cells into nude mice was used to evaluate tumor growth in vivo.Re-sults:GTF3C2 expression was upregulated in HCC tissues and was positively correlated with advanced tumor stages and high tumor grades.HCC patients with high GTF3C2 ex-pression had significantly worse survival outcomes.Knock-down of GTF3C2 suppressed the proliferation of Hep3B and HCCLM3 cells,while overexpression of GTF3C2 facilitated the proliferation of SNU449 and Huh7 cells.GTF3C2 promoted USP21 expression by activating its transcription,which sub-sequently increased the levels of MEK2 and p-ERK1/2 in HCC cells.Overexpression of both USP21 and MEK2 counteracted the GTF3C2 knockdown-induced inactivation of the ERK1/2 pathway.Moreover,GTF3C2 promoted HCC cell proliferation in vitro and tumor growth in vivo by regulating the USP21/MEK2/ERK1/2 pathway.Conclusions:Upregulation of GT-F3C2 is frequently observed in HCC tissues and predicts poor prognosis.GTF3C2 promotes HCC cell proliferation via the USP21/MEK2/ERK1/2 pathway.
