Qiao Huai-Yu, Zhang Qi, Wang Jia-Mei, Jiang Jing-Yi, Huyan Ling-Yue, Yan Jing, Li Chao, Wang Hua-Qin
Department of Biochemistry & Molecular Biology, China Medical University, Shenyang, 110026, China.
Criminal Investigation Police University of China, Shenyang, 110854, China.
Cancer Lett. 2022 Mar 31;529:85-99. doi: 10.1016/j.canlet.2021.12.029. Epub 2021 Dec 29.
Ovarian cancer (OC) is a common gynecological malignant tumor that seriously endangers the health of women worldwide. Tripartite motif containing 29 (TRIM29) is a TRIM family member that is frequently overexpressed in OC. However, the specific role of TRIM29 in OC remains obscure. To investigate the underlying molecular mechanism, a global proteomics analysis identified SET binding protein 1 (SETBP1) as a crucial target of TRIM29. Subsequently, the SETBP1/SET/Protein phosphatase 2 (PP2A) axis was confirmed to be required for the recovery of cancer stem cell (CSC)-like phenotype suppressed by TRIM29 knockdown. Mechanistically, TRIM29 facilitated SETBP1 transcriptional activation via the VEZF1 transcription factor. More importantly, TRIM29 promoted VEZF1 mRNA translation by recruiting RNA binding protein BICC1 to its 3'UTR. The clinical significance was established by the association of TRIM29 and SETBP1 expression with clinicopathological features in OC samples. The SETBP1/SET/PP2A axis driven by TRIM29 via transcription factor VEZF1 is at least one of the primary mechanisms underlying TRIM29 maintenance of the CSC-like characteristics in OC.
卵巢癌（OC）是一种常见的妇科恶性肿瘤，严重威胁着全球女性的健康。含三联基序蛋白29（TRIM29）是TRIM家族成员，在OC中经常过度表达。然而，TRIM29在OC中的具体作用仍不清楚。为了研究其潜在的分子机制，一项全局蛋白质组学分析确定SET结合蛋白1（SETBP1）是TRIM29的关键靶点。随后，证实SETBP1/SET/蛋白磷酸酶2（PP2A）轴是恢复因TRIM29敲低而被抑制的癌症干细胞（CSC）样表型所必需的。机制上，TRIM29通过VEZF1转录因子促进SETBP1的转录激活。更重要的是，TRIM29通过将RNA结合蛋白BICC1招募到其3'非翻译区来促进VEZF1 mRNA的翻译。通过TRIM29和SETBP1表达与OC样本临床病理特征的关联确定了其临床意义。TRIM29通过转录因子VEZF1驱动的SETBP1/SET/PP2A轴至少是TRIM29维持OC中CSC样特征的主要机制之一。
