Ovarian carcinoma is one of the most common malignant cancers in women. Previous research has shown that Smad4 participates in the progression of multiple biological reactions as a crucial regulator. Nevertheless, studies on the role of Smad4 in ovarian carcinoma have been extremely limited. The study aim was to explore the mechanism underlying Smad4 regulation of HO-8910 and SKOV3 cell viability and autophagy. We observed that Smad4 gene expression in ovarian carcinoma tissues and cell lines was downregulated, and Smad4 overexpression resulted in decreased proliferation and increased autophagy in HO-8910 and SKOV3 cells (ovarian carcinoma cells). We also found that Smad4 overexpression induced apoptosis of ovarian carcinoma cells. A co-immunoprecipitation assay also revealed that Smad4 interacted with the P85 subunit of PI3K and caused its degradation and dephosphorylation. Subsequently, expression of mTOR was inhibited. Accordingly, these findings showed that further investigation of the biological mechanisms underlying ovarian carcinoma occurrence and progression is warranted, which may lead to new ovarian carcinoma treatment strategies.

Impact statement

This study investigated the effect and mechanism of Smad4 in ovarian carcinoma (OC) cell viability and demonstrated that Smad4 acted as a tumor suppressor in OC, which may contribute to the understanding of molecular mechanisms underlying OC occurrence and progression. Smad4 expression was decreased in the OC specimens, but Smad4 recovery in the OC cell lines impaired the survival and viability of OC cells by increasing autophagy and apoptosis. Further investigation showed that Smad4 interacted with the P85 subunit of PI3K and caused deactivation of the PI3K/mTOR pathway. Therefore, Smad4 could be considered as a target in cancer therapy due to its regulatory effect in OC carcinogenesis.

中文翻译：

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亮点文章：Smad4通过PI3K-mTOR参与在HO-8910和SKOV3卵巢癌细胞系中诱导细胞死亡。

卵巢癌是女性中最常见的恶性肿瘤之一。先前的研究表明，Smad4作为重要的调节剂参与多种生物反应的进程。然而，关于Smad4在卵巢癌中的作用的研究非常有限。本研究的目的是探索HO-8910的Smad4调控以及SKOV3细胞活力和自噬的潜在机制。我们观察到Smad4基因在卵巢癌组织和细胞系中的表达下调，而Smad4的过表达导致HO-8910和SKOV3细胞（卵巢癌细胞）的增殖减少和自噬增加。我们还发现Smad4过表达诱导卵巢癌细胞凋亡。免疫共沉淀试验还显示，Smad4与PI3K的P85亚基相互作用，并导致其降解和去磷酸化。随后，mTOR的表达被抑制。因此，这些发现表明，有必要进一步研究卵巢癌发生和发展的生物学机制，这可能会导致新的卵巢癌治疗策略。

影响陈述

这项研究调查了Smad4在卵巢癌（OC）细胞活力中的作用和机制，并证明Smad4在OC中起着抑癌作用，这可能有助于理解OC发生和发展的分子机制。Smad4表达在OC标本中降低，但OC细胞系中Smad4的恢复通过增加自噬和凋亡而损害OC细胞的存活和生存能力。进一步的研究表明，Smad4与PI3K的P85亚基相互作用，并导致PI3K / mTOR通路失活。因此，由于Smad4对OC致癌作用的调节作用，可以将其视为癌症治疗的靶标。