Journal
MOLECULAR MEDICINE REPORTS
Volume 16, Issue 3, Pages 3194-3200Publisher
SPANDIDOS PUBL LTD
DOI: 10.3892/mmr.2017.6986
Keywords
nucleus accumbens-associated protein 1; homeobox A9; drug resistance; apoptosis; colorectal carcinoma
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Colorectal carcinoma (CRC) is one of the most common types of malignancy worldwide. Recently, neoadjuvant chemotherapy has become an important treatment strategy for CRC. However, treatment frequently fails due to the development of chemoresistance, which is a major obstacle for positive prognosis. However, the underlying mechanisms of chemoresistance remain unclear. The present study assessed the functions of nucleus accumbens-associated protein 1 (NAC1), an important transcriptional regulator, in CRC progression. Reverse transcription-quantitative polymerase chain reaction, western blot analysis and immunohistochemistry were performed to detect the expression levels of NAC1. It was identified that NAC1 was significantly overexpressed in CRC compared with non-tumorous tissues, indicating an oncogenic role. Following this, gain and loss of function analyses were performed in vitro to further investigate the function of NAC1. Cell viability and caspase-3/7 activity assays were used to assess chemotherapy-induced apoptosis. These results indicated that overexpression of NAC1 in CRC cells increased resistance to chemotherapy and inhibited apoptosis. Additionally, RNA interference-mediated knockdown of NAC1 restored the chemosensitivity of CRC cells. Furthermore, mechanistic investigation revealed that NAC1 increased drug resistance via inducing homeobox A9 (HOXA9) expression, and that knockdown of HOXA9 abrogated NAC1-induced drug resistance. In conclusion, the results of the present study demonstrated that NAC1 may be a critical factor in the development of chemoresistance, offering a potential novel target for the treatment of CRC.
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