Fork-head box protein M1(FoxM1)is a transcriptional factor which plays critical roles in cancer development and progression.However,the general regulatory mechanism of FoxM1 is still limited.STMN1 is a microtubule-bin...Fork-head box protein M1(FoxM1)is a transcriptional factor which plays critical roles in cancer development and progression.However,the general regulatory mechanism of FoxM1 is still limited.STMN1 is a microtubule-binding protein which can inhibit the assembly of microtubule dimer or promote depolymerization of microtubules.It was reported as a major responsive factor of paclitaxel resistance for clinical chemotherapy of tumor patients.But the function of abnormally high level of STMN1 and its regulation mechanism in cancer cells remain unclear.In this study,we used public database and tissue microarrays to analyze the expression pattern of FoxM1 and STMN1 and found a strong positive correlation between FoxM1 and STMN1 in multiple types of cancer.Lentivirus-mediated FoxM1/STMN1-knockdown cell lines were established to study the function of FoxM1/STMN1 by performing cell viability assay,plate clone formation assay,soft agar assay in vitro and xenograft mouse model in vivo.Our results showed that FoxMl promotes cell proliferation by upregulating STMN1.Further ChIP assay showed that FoxM1 upregulates STMN1 in a transcriptional level.Prognostic analysis showed that a high level of FoxM1 and STMN1 is related to poor prognosis in solid tumors.Moreover,a high co-expression of FoxM1 and STMN1 has a more significant correlation with poor prognosis.Our findings suggest that a general FoxMl-STMN1 axis contributes to cell proliferation and tumorigenesis in hepatocellular carcinoma,gastric cancer and colorectal cancer.The combination of FoxM1 and STMN1 can be a more precise biomarker for prognostic prediction.展开更多
基金supported by the National Natural Science Foundation of China(grantnumbers 81630069,81421003,31771439,81773262,81572763,81672751)the National Key Research and Development Program(grant number 2016YFC1303200)+1 种基金the Key Research and Development Program of Shaanxi(2019SF-010)Opening Projects of the State Key Laboratory of Cancer Biology(CBSKL201703,CBSKL201704,CBSKL201726)。
文摘Fork-head box protein M1(FoxM1)is a transcriptional factor which plays critical roles in cancer development and progression.However,the general regulatory mechanism of FoxM1 is still limited.STMN1 is a microtubule-binding protein which can inhibit the assembly of microtubule dimer or promote depolymerization of microtubules.It was reported as a major responsive factor of paclitaxel resistance for clinical chemotherapy of tumor patients.But the function of abnormally high level of STMN1 and its regulation mechanism in cancer cells remain unclear.In this study,we used public database and tissue microarrays to analyze the expression pattern of FoxM1 and STMN1 and found a strong positive correlation between FoxM1 and STMN1 in multiple types of cancer.Lentivirus-mediated FoxM1/STMN1-knockdown cell lines were established to study the function of FoxM1/STMN1 by performing cell viability assay,plate clone formation assay,soft agar assay in vitro and xenograft mouse model in vivo.Our results showed that FoxMl promotes cell proliferation by upregulating STMN1.Further ChIP assay showed that FoxM1 upregulates STMN1 in a transcriptional level.Prognostic analysis showed that a high level of FoxM1 and STMN1 is related to poor prognosis in solid tumors.Moreover,a high co-expression of FoxM1 and STMN1 has a more significant correlation with poor prognosis.Our findings suggest that a general FoxMl-STMN1 axis contributes to cell proliferation and tumorigenesis in hepatocellular carcinoma,gastric cancer and colorectal cancer.The combination of FoxM1 and STMN1 can be a more precise biomarker for prognostic prediction.
