Elevated expression of HSF1 promotes the progression of colorectal cancer by activating CLDN3 transcription

Yanxi Shao, Ting Ma, Dening Ma, Lue Hong, Min Lv, Shiqi Zhou, Zhibin Fang, Enyan Yu,  Xia Li,  Yuping Zhu

Abstract:

Colorectal cancer (CRC) is the most common gastrointestinal malignancy worldwide, with increasing morbidity and mortality. Heat shock transcription factor 1 (HSF1), as an important transcription factor regulating the expression of heat shock proteins, has been proven to play a crucial role in the development of various tumors. Yet the potential mechanism and clinical significance of HSF1 in CRC remain unclear and require further exploration. We used TCGA database to understand the clinical significance of HSF1 in CRC. Then, we verified the expression of HSF1 in CRC tissues by immunohistochemistry and analyzed its clinical significance. By constructing stable knockdown and overexpressed of HSF1 in cell lines to investigate the potential mechanisms of HSF1 to regulate CRC cell proliferation, migration, and invasion in vivo and in vitro. Next, differential genes expressed by HSF1 in CRC were analyzed by bioinformatics technology, and their correlation and interaction were verified by PCR, WB, and CHIP experiments. We confirmed that HSF1 is highly expressed in CRC and its upregulation is associated with poor prognosis of malignant events in CRC. Functionally, HSF1 can enhance the proliferation, invasion, and migration of CRC cell lines. In vivo experiments have shown that knockdown of HSF1 can inhibit tumor growth. In terms of molecular mechanism, we found that HSF1 can directly bind to the transcription factor binding site of CLDN3 and activate its transcription. Our research demonstrates the clinical significance and carcinogenic effect of HSF1. The functional mechanisms of HSF1 and its targets may serve as diagnostic and therapeutic targets for CRC.