Knocking down RAD51AP1 enhances chemosensitivity by inhibiting the self-renewal of CD133 positive ovarian cancer stem-like cells
Year: 2024
Type: article
Abstract: This study was designed to investigate the function of RAD51AP1 in the self-renewal and chemosensitivity of CD133 positive (CD133 + ) ovarian cancer (OC) stem-like cells. CD133 + (CD133 positive) OVCAR4 and CD133 negative (CD133 − ) OVCAR4 cells were separated from OVCAR4 by flow cytometry. Then, the separated CD133 + OVCAR4 cells were divided into the following groups: Vector group; RAD51AP1 group; siNC group; si-RAD51AP1 group. Next, sphere-formation assay and colony forming assay were used to evaluate the self-renewal and proliferation ability of cells; western blot to detect the expression of RAD51AP1, transforming growth factor beta 1 (TGF-β1) and SMAD4 proteins in tissues and cells; qRT-PCR to assess the mRNA levels of sex-determining region Y-box 2 (SOX2), octamer-binding transcription factor 4 (OCT4), NANOG and Kruppel-like factor 4 (KLF4). The performance of CD133 + OVCAR4 cells was much better than that of CD133 − OVCAR4 cells in sphere-formation assay and colony forming assay. Besides, compared with adjacent group and CD133 − OVCAR4 cells, the expression level of RAD51AP1 increased significantly in OC group and CD133 + OVCAR4 cells. Moreover, the over-expression of RAD51AP1 promoted the self-renewal and proliferation of CD133 + OVCAR4 cells. On the contrary, knocking down the expression level of RAD51AP1 could inhibit the self-renewal and proliferation of CD133 + OVCAR4 cells and improve the sensitivity of cells to chemotherapy drugs. The findings of this study showed that RAD51AP1 was highly expressed in OC tissue and CD133 + OVCAR4 cells, and regulated the self-renewal and chemosensitivity of tumor cells through the TGF-β1/SMAD4 signaling pathway.
Source: Discover Oncology
Authors: Si-heng Zeng, Zhi-qiang Yan, Qing Ren, Li-hui Lin, Zhen Chen
Language: English
Topic: Cancer Cells and Metastasis
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $1,590
OpenAlex ID: W4402270266