Objective Accumulating evidence suggests that transmembrane 4 L6 family member 1(TM4SF1)is associated with the development of various cancers;yet comprehensive studies on TM4SF1 in cervical cancer are lacking.Therefor...Objective Accumulating evidence suggests that transmembrane 4 L6 family member 1(TM4SF1)is associated with the development of various cancers;yet comprehensive studies on TM4SF1 in cervical cancer are lacking.Therefore,we aimed to evaluate the prognostic value of TM4SF1 in cervical cancer,elucidate its potential oncogenic functions in this disease,and further explore its feasibility as a therapeutic target.Methods The expression profiles and clinical information of cervical cancer patients were obtained from The Cancer Genome Atlas(TCGA)database.The expression levels of TM4SF1 were compared between cervical cancer and normal cervical tissues using the Wilcoxon rank-sum test.Kaplan–Meier analysis was employed to assess the prognostic value of TM4SF1.Furthermore,functional enrichment analyses were performed to explore the associated signaling pathways and biological functions.The methylation status of TM4SF1 was analyzed using the UALCAN and MethSurv databases.In addition,in vitro experiments were conducted to preliminarily validate the role and mechanisms of TM4SF1 in cervical cancer.Results TM4SF1 was overexpressed in nearly all tumors,and its overexpression was associated with poor prognosis in cervical cancer.Moreover,the correlation between TM4SF1 expression and the expression of immune cell infiltration markers and immune checkpoint genes suggested that it had potential applications in cancer immunotherapy.Western blot analysis and immunohistochemistry revealed significantly elevated protein levels of TM4SF1 in cervical cancer tissues and cells.Further studies revealed that the knockdown of TM4SF1 significantly inhibited the migration,invasion,and epithelial-mesenchymal transition(EMT)of HeLa and SiHa cells,as well as promoted their apoptosis.Conclusion TM4SF1 may serve as a potential prognostic biomarker and therapeutic target for cervical cancer.展开更多
Background:Kinesin-14 family protein 1(KIFC1)is abnormally overexpressed in various cancers,and the transcription factor ETS variant 1(ETV1)is an oncogenic transcription factor in tumors.The potential binding sites on...Background:Kinesin-14 family protein 1(KIFC1)is abnormally overexpressed in various cancers,and the transcription factor ETS variant 1(ETV1)is an oncogenic transcription factor in tumors.The potential binding sites on the KIFC1 promoter by ETV1 were observed;however,no evidence supports that ETV1 targets KIFC1.Aims:This study aimed to investigate the relationship between KIFC1 and ETV1,and their effects and mechanisms in pancreatic cancer.Methods:Pan-cancer analysis of KIFC1 expression was performed in GEPIA2 database.KIFC1 expression levels were determined by immunohistochemistry(IHC)in our pancreatic cancer cohort.The correlation between KIFC1 expression and prognosis,tumor mutation burden,tumor purity,mismatch repair,and high-frequency tumor mutated genes was analyzed using a series of bioinformatic tools.ETV1 targeting of KIFC1 promoter transcription was determined using luciferase reporter assay.KIFC1 knockdown and ETV1 overexpression were used to determine the role of the ETV1/KIFC1 axis in cell proliferation,migration,invasion,and epithelial-mesenchymal transition(EMT)of pancreatic cancer cells in vitro and tumor growth in vivo.Result:KIFC1 expression was increased in clinical specimens and pancreatic cancer cell lines and positively correlated with tumor mutation burden,tumor purity,mismatch repair,and KRAS and TP53 mutations.High KIFC1 expression was significantly associated with poor prognosis.Knockdown of KIFC1 suppressed the proliferation,migration,and invasion of pancreatic cancer cells and tumor growth.ETV1 overexpression increased KIFC1 expression and affected KIFC1 transcription.ETV1 overexpression reversed the role of KIFC1 knockdown in inhibiting cell proliferation,invasion,migration,and EMT,as validated in vivo.Conclusions:KIFC1 serves as a tumor activator in pancreatic cancer by promoting proliferation,migration,invasion,and tumor growth,which may be partly manipulated by ETV1.展开更多
基金the Natural Science Fund of Hubei Province(No.2022CFC019 and No.2021CFB430).
文摘Objective Accumulating evidence suggests that transmembrane 4 L6 family member 1(TM4SF1)is associated with the development of various cancers;yet comprehensive studies on TM4SF1 in cervical cancer are lacking.Therefore,we aimed to evaluate the prognostic value of TM4SF1 in cervical cancer,elucidate its potential oncogenic functions in this disease,and further explore its feasibility as a therapeutic target.Methods The expression profiles and clinical information of cervical cancer patients were obtained from The Cancer Genome Atlas(TCGA)database.The expression levels of TM4SF1 were compared between cervical cancer and normal cervical tissues using the Wilcoxon rank-sum test.Kaplan–Meier analysis was employed to assess the prognostic value of TM4SF1.Furthermore,functional enrichment analyses were performed to explore the associated signaling pathways and biological functions.The methylation status of TM4SF1 was analyzed using the UALCAN and MethSurv databases.In addition,in vitro experiments were conducted to preliminarily validate the role and mechanisms of TM4SF1 in cervical cancer.Results TM4SF1 was overexpressed in nearly all tumors,and its overexpression was associated with poor prognosis in cervical cancer.Moreover,the correlation between TM4SF1 expression and the expression of immune cell infiltration markers and immune checkpoint genes suggested that it had potential applications in cancer immunotherapy.Western blot analysis and immunohistochemistry revealed significantly elevated protein levels of TM4SF1 in cervical cancer tissues and cells.Further studies revealed that the knockdown of TM4SF1 significantly inhibited the migration,invasion,and epithelial-mesenchymal transition(EMT)of HeLa and SiHa cells,as well as promoted their apoptosis.Conclusion TM4SF1 may serve as a potential prognostic biomarker and therapeutic target for cervical cancer.
文摘Background:Kinesin-14 family protein 1(KIFC1)is abnormally overexpressed in various cancers,and the transcription factor ETS variant 1(ETV1)is an oncogenic transcription factor in tumors.The potential binding sites on the KIFC1 promoter by ETV1 were observed;however,no evidence supports that ETV1 targets KIFC1.Aims:This study aimed to investigate the relationship between KIFC1 and ETV1,and their effects and mechanisms in pancreatic cancer.Methods:Pan-cancer analysis of KIFC1 expression was performed in GEPIA2 database.KIFC1 expression levels were determined by immunohistochemistry(IHC)in our pancreatic cancer cohort.The correlation between KIFC1 expression and prognosis,tumor mutation burden,tumor purity,mismatch repair,and high-frequency tumor mutated genes was analyzed using a series of bioinformatic tools.ETV1 targeting of KIFC1 promoter transcription was determined using luciferase reporter assay.KIFC1 knockdown and ETV1 overexpression were used to determine the role of the ETV1/KIFC1 axis in cell proliferation,migration,invasion,and epithelial-mesenchymal transition(EMT)of pancreatic cancer cells in vitro and tumor growth in vivo.Result:KIFC1 expression was increased in clinical specimens and pancreatic cancer cell lines and positively correlated with tumor mutation burden,tumor purity,mismatch repair,and KRAS and TP53 mutations.High KIFC1 expression was significantly associated with poor prognosis.Knockdown of KIFC1 suppressed the proliferation,migration,and invasion of pancreatic cancer cells and tumor growth.ETV1 overexpression increased KIFC1 expression and affected KIFC1 transcription.ETV1 overexpression reversed the role of KIFC1 knockdown in inhibiting cell proliferation,invasion,migration,and EMT,as validated in vivo.Conclusions:KIFC1 serves as a tumor activator in pancreatic cancer by promoting proliferation,migration,invasion,and tumor growth,which may be partly manipulated by ETV1.
