NHC Key Laboratory of Molecular Probes and Targeted Diagnosis and Therapy, Harbin Medical University, Harbin, China.
Department of Urology (Heilongjiang Key Laboratory of Scientific Research in Urology), The Fourth Hospital of Harbin Medical University, Harbin, China.
FASEB J. 2023 Sep;37(9):e23118. doi: 10.1096/fj.202201880R.
Renal cancer stem cells (RCSCs) derived from clear cell renal cell carcinoma (ccRCC) tissues with higher microvessel density (MVD) have strong stemness and endothelial progenitor cells-like (EPCs-like) characteristics. A high level of lncRNA PVT1 expression is essential for simultaneously retaining strong RCSC stemness and EPCs-like characteristics. PVT1 binds with TAZ protein and prevents its phosphorylation, which promotes RCSC stemness. Moreover, RCSCs support endothelial differentiation and angiogenesis, which are mediated via the PVT1/miR-15b/KDR axis. This report provides insight into the determinants of RCSC impact on stemness and highlights the critical role of RCSC in angiogenesis. The presented findings suggest that targeting RCSC through PVT1 expression may be a new treatment strategy for ccRCC.
来源于高微血管密度（MVD）的透明细胞肾细胞癌（ccRCC）组织的肾肿瘤干细胞（RCSCs）具有较强的干细胞特性和内皮祖细胞样（EPCs-like）特征。高水平的长链非编码 RNA PVT1 的表达对于同时保留强大的 RCSC 干细胞特性和 EPCs-like 特征是必需的。PVT1 与 TAZ 蛋白结合并阻止其磷酸化，从而促进 RCSC 干细胞特性。此外，RCSCs 通过 PVT1/miR-15b/KDR 轴支持内皮细胞分化和血管生成。本报告深入了解了 RCSC 对干细胞特性影响的决定因素，并强调了 RCSC 在血管生成中的关键作用。研究结果表明，通过 PVT1 表达靶向 RCSC 可能是治疗 ccRCC 的一种新策略。
