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SHCBP1 promotes cisplatin resistance and progression of LSCC through POU2F1-mediated transcriptional activation
Mian Dai1, Gang Qin2, Yundan Bai2,3
1Department of Health Management Medical Center, Chengdu Integrated TCM&Western Medicine Hospital, Chengdu, Sichuan, China.
Abstract:
This study aimed to investigate the role of Src homology collagen-binding protein 1 (SHCBP1) in the progression and cisplatin resistance of laryngeal squamous cell carcinoma (LSCC), and to elucidate the underlying regulatory mechanism. LSCC cell lines were used to assess SHCBP1 expression by western blotting and quantitative real-time PCR (qRT-PCR). SHCBP1 knockdown was achieved by siRNA transfection, and its effects on cell proliferation, migration, and cisplatin sensitivity were evaluated through cell viability assays, wound healing assays, and flow cytometry. The transcriptional regulation of SHCBP1 by POU class 2 homeobox 1 (POU2F1) was investigated using dual-luciferase reporter assays and chromatin immunoprecipitation (ChIP) analysis. In vivo, tumor xenograft models were established to determine the impact of SHCBP1 knockdown on tumor growth and cisplatin responsiveness. SHCBP1 was highly expressed in LSCC cells, and its knockdown significantly inhibited LSCC cell proliferation and migration. Moreover, SHCBP1 silencing enhanced the sensitivity of LSCC cells to cisplatin treatment. Mechanistically, POU2F1 was shown to activate SHCBP1 transcription in LSCC cells. In vivo experiments further confirmed that SHCBP1 knockdown suppressed tumor growth and metastasis and increased cisplatin sensitivity. Overall, SHCBP1 contributes to LSCC cisplatin resistance and progression by promoting POU2F1-mediated transcriptional activation.
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