SPZ1 promotes deregulation of Bim to boost apoptosis resistance in colorectal cancer

• DOI: 10.1042/cs20190865
• Publication Date: 2020-01-14T11:49:36Z
• Authors: Xiao-Yu Liu; Chang-Bo Zheng; Teng Wang; Jian Xu; Meng Zhang; Ling-Shan Gou; Linfang Jin; Xiaowei Qi; Xianhai Zeng; Hongwen Li; Shuqi Qiu; Peng Zhang
• Keywords: Mitogen-Activated Protein Kinase 1; Mitogen-Activated Protein Kinase 3; Bcl-2-Like Protein 11; Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; Mice, Nude; Apoptosis; Neoplasms, Experimental; Up-Regulation; 3. Good health; Gene Expression Regulation, Neoplastic; 03 medical and health sciences; 0302 clinical medicine; Cell Line, Tumor; Gene Knockdown Techniques; Biomarkers, Tumor; Animals; Heterografts; Humans; Fluorouracil; RNA, Small Interfering; Colorectal Neoplasms; Cell Proliferation

Abstract Colorectal cancer (CRC) is the third most common malignancies in adults. Similar to other solid tumors, CRC cells show increased proliferation and suppressed apoptosis during development progression of disease. Previous studies have shown that a novel tumor oncogene, spermatogenic basic helix-loop-helix transcription factor zip 1 (SPZ1), can promote proliferation. However, it unclear whether SPZ1 plays role suppressing apoptosis, molecular mechanism behind SPZ1’s suppression remains unclear. Here, we found silencing endogenous inhibits cell growth induces overexpression promotes growth. These findings were corroborated by vitro vivo studies. Interestingly, overexpressing resistant 5-fluorouracil, drug commonly used treat cancer. Moreover, knocking down led activation caspase through deregulation Bim ERK1/2, tissues had significantly higher lower expression, SPZ1HBimL associated with advanced clinical stage CRC. Collectively, our demonstrate contributes limiting apoptosis. reduces altering stability Bim, suggesting may serve as biomarker therapeutic target for