The lncRNA TPTEP1 suppresses PI3K/AKT signalling and inhibits ovarian cancer progression by interacting with PTBP1

Yifan Feng, Zhe Zhang, Huijun Yang, Fulu Miao, Yuyang Li, Minmin Zhang, Yunxia Cao, Min Li
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Abstract

The expression of the long noncoding RNA (lncRNA) TPTE pseudogene 1 (TPTEP1) is significantly downregulated in ovarian cancer (OC). However, the function and mechanism of the lncRNA TPTEP1 in OC have not been identified. To investigate the expression of the lncRNA TPTEP1, we analysed a publicly available dataset and 20 pairs of OC and normal ovarian samples tissue from the First Affiliated Hospital of Anhui Medical University. Functional assays were used to determine the role of the lncRNA TPTEP1 in OC progression. Furthermore, Western blot, FISH, RNA pull-down, mass spectrometry and RNA immunoprecipitation approaches were used to determine the mechanism by which the lncRNA TPTEP1 affects OC progression. Animal experiments were used to determine the role of the lncRNA TPTEP1 in ovarian tumorigenicity in vivo. The expression of the lncRNA TPTEP1 in OC tissues was significantly lower than that in normal tissues and low expression of the lncRNA TPTEP1 was significantly correlated with advanced FIGO stage and the presence of malignant ascites in OC patients. In vitro and in vivo, regulation of the expression of the lncRNA TPTEP1 caused changes in OC cell proliferation, migration, invasion and apoptosis. Mechanistically, we found that TPTEP1 directly binds to the polypyrimidine tract-binding protein 1 (PTBP1) protein and inhibits PI3K/AKT signalling. The lncRNA TPTEP1 inhibits PI3K/AKT signalling by directly binding PTBP1, possibly indicating the molecular mechanism underlying its biological function. With further research, these findings may aid in the development of clinically useful strategies for the treatment of OC.

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lncRNA TPTEP1 通过与 PTBP1 相互作用抑制 PI3K/AKT 信号并抑制卵巢癌的进展
长非编码 RNA(lncRNA)TPTE 伪基因 1(TPTEP1)在卵巢癌(OC)中的表达明显下调。然而,lncRNA TPTEP1在OC中的功能和机制尚未确定。为了研究lncRNA TPTEP1的表达,我们分析了一个公开的数据集和20对来自安徽医科大学第一附属医院的OC和正常卵巢样本组织。通过功能检测确定了 lncRNA TPTEP1 在卵巢癌进展中的作用。此外,还采用了Western印迹、FISH、RNA牵引、质谱和RNA免疫沉淀等方法来确定lncRNA TPTEP1影响OC进展的机制。通过动物实验确定了 lncRNA TPTEP1 在体内卵巢致瘤性中的作用。lncRNA TPTEP1在OC组织中的表达量明显低于正常组织,lncRNA TPTEP1的低表达与OC患者的FIGO分期晚期和恶性腹水的存在明显相关。在体外和体内,lncRNA TPTEP1的表达调控引起了OC细胞增殖、迁移、侵袭和凋亡的变化。从机理上讲,我们发现TPTEP1直接与多嘧啶束结合蛋白1(PTBP1)蛋白结合,抑制PI3K/AKT信号传导。lncRNA TPTEP1通过直接结合PTBP1抑制PI3K/AKT信号传导,这可能表明了其生物学功能的分子机制。随着研究的深入,这些发现可能有助于开发临床上有用的OC治疗策略。
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期刊介绍: The Journal of Cellular and Molecular Medicine serves as a bridge between physiology and cellular medicine, as well as molecular biology and molecular therapeutics. With a 20-year history, the journal adopts an interdisciplinary approach to showcase innovative discoveries. It publishes research aimed at advancing the collective understanding of the cellular and molecular mechanisms underlying diseases. The journal emphasizes translational studies that translate this knowledge into therapeutic strategies. Being fully open access, the journal is accessible to all readers.
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