Background:Homeobox B8(HOXB8),a member of HOX family,plays a key role in the development of colorectal cancer(CRC).However,the function of HOXB8 in oxaliplatin(OXA)resistance in CRC is still unclear.This study investi...Background:Homeobox B8(HOXB8),a member of HOX family,plays a key role in the development of colorectal cancer(CRC).However,the function of HOXB8 in oxaliplatin(OXA)resistance in CRC is still unclear.This study investigated the role and precise molecular mechanism of HOXB8 in OXA-resistant CRC cells.Methods:The cell viability was measured by the 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide(MTT)assay,and the colony forming ability was determined by colony formation assay.The silencing RNA(siRNA)approach was used to knockdown HOXB8 in CRC cells while the lentiviral transfection system was used to establish stable HOXB8 overexpressing CRC cells.The protein and mRNA levels were evaluated by western blot and real-time reverse transcription-polymerase chain reaction.Results:HOXB8 expression was upregulated in OXA-resistant HCT116 cells(HCT116/OXA)compared to its level in the parent HCT116 cells.Knockdown of HOXB8 significantly inhibited CRC cell growth by suppressing the signal transducer and activator of transcription 3(STAT3)pathway.HOXB8 knockdown also potentiated cytotoxicity of OXA in CRC cells.Inversely,HOXB8 overexpression attenuated OXAinduced growth inhibition of HCT116 cells and RKO cells by activating STAT3 signaling.HOXB8 knockdown effectively inhibited HCT116/OXA cell viability regardless of OXA treatment by suppressing STAT3 signaling.Conclusions:These results shed light on the important functions of HOXB8 in OXA-resistant CRC and suggested that targeting HOXB8 might be an effective therapeutic strategy for select OXA-resistant CRC patients.展开更多
Gliomas are the most commonly occurring tumors of the central nervous system. Glioblastoma multiforme (GBM) is the most malignant and aggressive brain cancer in adults. Further understanding of the mechanisms underlyi...Gliomas are the most commonly occurring tumors of the central nervous system. Glioblastoma multiforme (GBM) is the most malignant and aggressive brain cancer in adults. Further understanding of the mechanisms underlying the aggressive nature of GBM is urgently needed. Here we identified homeobox B8(HOXB8), a member of the homeobox family, as a crucial contributor to the aggressiveness of GBM. Data mining of publicly accessible RNA sequence datasets and our patient cohorts confirmed a higher expression of HOXB8 in the tumor tissue of GBM patients, and a strong positive correlation between the expression level and pathological grading of tumors and a negative correlation between the expression level and the overall survival rate. We next showed that HOXB8 promotes the proliferation and migration of glioblastoma cells and is crucial for the activation of the PI3K/AKT pathway and expression of epithelial–mesenchymal transition-related genes, possibly through direct binding to the promoter of SAMD9 (Sterile Alpha Motif Domain-Containing Protein 9) and activating its transcription. Collectively, we identified HOXB8 as a critical contributor to the aggressiveness of GBM, which provides insights into a potential therapeutic target for GBM and opens new avenues for improving its treatment outcome.展开更多
基金supported by the Natural Science Foundation of Zhejiang Province(LZ22H160006)Huadong Medicine Joint Funds of the Zhejiang Provincial Natural Science Foundation of China(LHDMY22H160002)Wenzhou Municipal Science and Technology Bureau(Y20180085).
文摘Background:Homeobox B8(HOXB8),a member of HOX family,plays a key role in the development of colorectal cancer(CRC).However,the function of HOXB8 in oxaliplatin(OXA)resistance in CRC is still unclear.This study investigated the role and precise molecular mechanism of HOXB8 in OXA-resistant CRC cells.Methods:The cell viability was measured by the 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide(MTT)assay,and the colony forming ability was determined by colony formation assay.The silencing RNA(siRNA)approach was used to knockdown HOXB8 in CRC cells while the lentiviral transfection system was used to establish stable HOXB8 overexpressing CRC cells.The protein and mRNA levels were evaluated by western blot and real-time reverse transcription-polymerase chain reaction.Results:HOXB8 expression was upregulated in OXA-resistant HCT116 cells(HCT116/OXA)compared to its level in the parent HCT116 cells.Knockdown of HOXB8 significantly inhibited CRC cell growth by suppressing the signal transducer and activator of transcription 3(STAT3)pathway.HOXB8 knockdown also potentiated cytotoxicity of OXA in CRC cells.Inversely,HOXB8 overexpression attenuated OXAinduced growth inhibition of HCT116 cells and RKO cells by activating STAT3 signaling.HOXB8 knockdown effectively inhibited HCT116/OXA cell viability regardless of OXA treatment by suppressing STAT3 signaling.Conclusions:These results shed light on the important functions of HOXB8 in OXA-resistant CRC and suggested that targeting HOXB8 might be an effective therapeutic strategy for select OXA-resistant CRC patients.
基金the National Natural Science Foundation of China(31571298).
文摘Gliomas are the most commonly occurring tumors of the central nervous system. Glioblastoma multiforme (GBM) is the most malignant and aggressive brain cancer in adults. Further understanding of the mechanisms underlying the aggressive nature of GBM is urgently needed. Here we identified homeobox B8(HOXB8), a member of the homeobox family, as a crucial contributor to the aggressiveness of GBM. Data mining of publicly accessible RNA sequence datasets and our patient cohorts confirmed a higher expression of HOXB8 in the tumor tissue of GBM patients, and a strong positive correlation between the expression level and pathological grading of tumors and a negative correlation between the expression level and the overall survival rate. We next showed that HOXB8 promotes the proliferation and migration of glioblastoma cells and is crucial for the activation of the PI3K/AKT pathway and expression of epithelial–mesenchymal transition-related genes, possibly through direct binding to the promoter of SAMD9 (Sterile Alpha Motif Domain-Containing Protein 9) and activating its transcription. Collectively, we identified HOXB8 as a critical contributor to the aggressiveness of GBM, which provides insights into a potential therapeutic target for GBM and opens new avenues for improving its treatment outcome.
