Roles of ZEB2 and RBM38 in liver cancer stem cell proliferation

• Published in: Journal of B.U.ON. : official journal of the Balkan Union of Oncology Vol. 25; no. 3; p. 1390
• Main Authors: Yu, Xiaowan, Wang, Wei, Lin, Xiaorong, Zheng, Xuecong, Yang, Anqi
• Format: Journal Article
• Language: English
• Published: Greece 01.05.2020
• Subjects: Animals; Cell Line, Tumor; Cell Movement - genetics; Cell Proliferation - genetics; Disease Models, Animal; Down-Regulation - genetics; Liver Neoplasms - genetics; Male; Mice; Mice, Inbred BALB C; Neoplastic Stem Cells - pathology; RNA-Binding Proteins - genetics; Tumor Microenvironment - genetics; Up-Regulation - genetics; Wnt Signaling Pathway - genetics; Zinc Finger E-box Binding Homeobox 2 - genetics
• ISSN: 2241-6293

Liver cancer stem cells are associated with tumor progression, metastasis, and resistance to chemotherapy. Therefore, it is important to understand the proteins that support the tumor microenvironment. The suppression of ZEB2 results from inactivation of the Wnt/β catenin pathway. Like RBM38, it suppresses tumor outgrowth and helps increase the survival of cancer patients. However, no studies have examined the direct roles of ZEB2 and RBM38 in the tumor microenvironment. We developed an early/advanced stage liver cancer mouse model using CD133+ cell injection that mimics liver cancer in all ways. Histology, Western blotting, and immunohistochemistry analyses were used to examine cancer progression. Histologically, the early liver cancer showed microfoci structures; the advanced cancer showed distinct morphological changes with enlarged nucleoli and cell clumping. Immunohistochemical and Western blotting analyses of CD133 and ZEB2 proteins showed similar upregulated expression as the tumor progressed. However, RBM38 expression increased dramatically in early liver cancer but was downregulated in advanced liver cancer. ZEB2 favors a tumor microenvironment that supports liver cancer stem cell proliferation, while RBM38 expression negatively affects the tumor microenvironment and restricts liver cancer stem cell proliferation.