BACKGROUND Monopolar spindle-binding protein 3B(MOB3B)functions as a signal transducer and altered MOB3B expression is associated with the development of human cancers.AIM To investigate the role of MOB3B in colorecta...BACKGROUND Monopolar spindle-binding protein 3B(MOB3B)functions as a signal transducer and altered MOB3B expression is associated with the development of human cancers.AIM To investigate the role of MOB3B in colorectal cancer(CRC).METHODS This study collected 102 CRC tissue samples for immunohistochemical detection of MOB3B expression for association with CRC prognosis.After overexpression and knockdown of MOB3B expression were induced in CRC cell lines,changes in cell viability,migration,invasion,and gene expression were assayed.Tumor cell autophagy was detected using transmission electron microscopy,while nude mouse xenograft experiments were performed to confirm the in-vitro results.RESULTS MOB3B expression was reduced in CRC vs normal tissues and loss of MOB3B expression was associated with poor CRC prognosis.Overexpression of MOB3B protein in vitro attenuated the cell viability as well as the migration and invasion capacities of CRC cells,whereas knockdown of MOB3B expression had the opposite effects in CRC cells.At the molecular level,microtubule-associated protein light chain 3 II/I expression was elevated,whereas the expression of matrix metalloproteinase(MMP)2,MMP9,sequestosome 1,and phosphorylated mechanistic target of rapamycin kinase(mTOR)was downregulated in MOB3B-overexpressing RKO cells.In contrast,the opposite results were observed in tumor cells with MOB3B knockdown.The nude mouse data confirmed these in-vitro findings,i.e.,MOB3B expression suppressed CRC cell xenograft growth,whereas knockdown of MOB3B expression promoted the growth of CRC cell xenografts.CONCLUSION Loss of MOB3B expression promotes CRC development and malignant behaviors,suggesting a potential tumor suppressive role of MOB3B in CRC by inhibition of mTOR/autophagy signaling.展开更多
BACKGROUND In patients with colorectal cancer(CRC),tumour metastasis is the leading cause of death.The search for key genes involved in metastasis of CRC is imperative for improved prognoses and treatments.SPDL1 has b...BACKGROUND In patients with colorectal cancer(CRC),tumour metastasis is the leading cause of death.The search for key genes involved in metastasis of CRC is imperative for improved prognoses and treatments.SPDL1 has been implicated in the deve-lopment of CRC,however,its mechanism of action remains unclear.AIM To investigate the role and mechanism of action by which SPDL1 inhibits the development and metastasis of CRC.METHODS In this study,we examined the relationship between SPDL1 expression and CRC prognosis using immunohistochemistry.Survival analyses were performed using Kaplan-Meier analysis and log-rank test.After knocking down SPDL1 in the HCT116 cancer cell line changes in cell viability,migration,invasion,and gene expression were examined using a cell counting kit 8 assay,Transwell assay,and Western blot.The effect of SPDL1 on the cell cycle was assessed using flow cy-tometry.RNA sequencing was used to analyse the effect of SPDL1 on gene expression of CRC cells.The mechanism of action of SPDL1 in CRC was further clarified using U0126,an inhibitor of the mitogen-activated protein kinase signaling pathway.RESULTS SPDL1 is expressed at low levels in tissues of patients with CRC,and this reduced expression is associated with poor prognosis.Functionally,low expression of SPDL1 in CRC promotes cell proliferation,migration,invasion,and affects the cell cycle.Mechanistically,SPDL1 affects the progression of CRC through its regulation of the process of epithelial-mesenchymal transition(EMT)and of the epidermal growth factor receptor(EGFR)/extracellular signal-regulated kinase(ERK)signaling pathways.CONCLUSION This study showed that the loss of SPDL1 may induce EMT and promote cell migration and invasion in CRC through the EGFR/ERK pathway.展开更多
基金Supported by National Natural Science Foundation of China,No.81760516Natural Science Foundation of Guangxi,China,No.2019GXNSFAA185030+1 种基金Self-Financed Scientific Research Projects of Guangxi Zhuang Autonomous Region Health and Family Planning Commission,China,No.Z20181003Guangxi Medical University Youth Science Fund Project,China,No.GXMUYSF202221.
文摘BACKGROUND Monopolar spindle-binding protein 3B(MOB3B)functions as a signal transducer and altered MOB3B expression is associated with the development of human cancers.AIM To investigate the role of MOB3B in colorectal cancer(CRC).METHODS This study collected 102 CRC tissue samples for immunohistochemical detection of MOB3B expression for association with CRC prognosis.After overexpression and knockdown of MOB3B expression were induced in CRC cell lines,changes in cell viability,migration,invasion,and gene expression were assayed.Tumor cell autophagy was detected using transmission electron microscopy,while nude mouse xenograft experiments were performed to confirm the in-vitro results.RESULTS MOB3B expression was reduced in CRC vs normal tissues and loss of MOB3B expression was associated with poor CRC prognosis.Overexpression of MOB3B protein in vitro attenuated the cell viability as well as the migration and invasion capacities of CRC cells,whereas knockdown of MOB3B expression had the opposite effects in CRC cells.At the molecular level,microtubule-associated protein light chain 3 II/I expression was elevated,whereas the expression of matrix metalloproteinase(MMP)2,MMP9,sequestosome 1,and phosphorylated mechanistic target of rapamycin kinase(mTOR)was downregulated in MOB3B-overexpressing RKO cells.In contrast,the opposite results were observed in tumor cells with MOB3B knockdown.The nude mouse data confirmed these in-vitro findings,i.e.,MOB3B expression suppressed CRC cell xenograft growth,whereas knockdown of MOB3B expression promoted the growth of CRC cell xenografts.CONCLUSION Loss of MOB3B expression promotes CRC development and malignant behaviors,suggesting a potential tumor suppressive role of MOB3B in CRC by inhibition of mTOR/autophagy signaling.
基金Supported by the Natural Science Foundation of Guangxi Province,No.2019GXNSFAA185030 and No.2023GXNSFBA026129the Scientific Research Project of the Second Affiliated Hospital of Guangxi Medical University,No.EFYKY2020013the Cultivation Science Foundation of the Second Affiliated Hospital of Guangxi Medical University,No.GJPY2023005 and No.GJPY2023009.
文摘BACKGROUND In patients with colorectal cancer(CRC),tumour metastasis is the leading cause of death.The search for key genes involved in metastasis of CRC is imperative for improved prognoses and treatments.SPDL1 has been implicated in the deve-lopment of CRC,however,its mechanism of action remains unclear.AIM To investigate the role and mechanism of action by which SPDL1 inhibits the development and metastasis of CRC.METHODS In this study,we examined the relationship between SPDL1 expression and CRC prognosis using immunohistochemistry.Survival analyses were performed using Kaplan-Meier analysis and log-rank test.After knocking down SPDL1 in the HCT116 cancer cell line changes in cell viability,migration,invasion,and gene expression were examined using a cell counting kit 8 assay,Transwell assay,and Western blot.The effect of SPDL1 on the cell cycle was assessed using flow cy-tometry.RNA sequencing was used to analyse the effect of SPDL1 on gene expression of CRC cells.The mechanism of action of SPDL1 in CRC was further clarified using U0126,an inhibitor of the mitogen-activated protein kinase signaling pathway.RESULTS SPDL1 is expressed at low levels in tissues of patients with CRC,and this reduced expression is associated with poor prognosis.Functionally,low expression of SPDL1 in CRC promotes cell proliferation,migration,invasion,and affects the cell cycle.Mechanistically,SPDL1 affects the progression of CRC through its regulation of the process of epithelial-mesenchymal transition(EMT)and of the epidermal growth factor receptor(EGFR)/extracellular signal-regulated kinase(ERK)signaling pathways.CONCLUSION This study showed that the loss of SPDL1 may induce EMT and promote cell migration and invasion in CRC through the EGFR/ERK pathway.
