Background
Chemoresistance remains a significant challenge in colorectal cancer (CRC) treatment, necessitating a deeper understanding of its underlying mechanisms. HOXC11 has emerged as a potential regulator in various cancers, but its role in CRC chemoresistance remains unclear.
Conclusions
In summary, our study reveals that HOXC11 regulates mitochondrial function through the modulation of mtDNA transcription, impacting chemoresistance in colorectal cancer cells. These findings underscore the significance of understanding the molecular mechanisms underlying chemoresistance and highlight the potential therapeutic implications of targeting mitochondrial function in CRC treatment.
Methods
Sulforhodamine B assay was employed to assess the cell viability of CRC cells following treatment with chemotherapeutic drugs. Immunofluorescence staining was performed to examine the subcellular localization of HOXC11 in normal and chemoresistant CRC cells. The Seahorse mito stress test was conducted to evaluate the mitochondrial respiratory function of CRC cells. Real-time PCR was utilized to measure the expression level and copy number of mitochondrial DNA (mtDNA).
Results
Our findings revealed that HOXC11 was overexpressed in CRC cells compared to normal colorectal cells and correlated with poorer prognosis in CRC patients. Knockout of HOXC11 reversed acquired chemoresistance in CRC cells. Furthermore, we observed a functional subset of HOXC11 localized to the mitochondria in chemoresistant CRC cells, which regulated mitochondrial function by modulating mtDNA transcription, thereby affecting chemoresistance. Conclusions: In summary, our study reveals that HOXC11 regulates mitochondrial function through the modulation of mtDNA transcription, impacting chemoresistance in colorectal cancer cells. These findings underscore the significance of understanding the molecular mechanisms underlying chemoresistance and highlight the potential therapeutic implications of targeting mitochondrial function in CRC treatment.