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 参与诱导 HO-8910 和 SKOV3 卵巢癌细胞系细胞死亡。

卵巢癌是女性最常见的恶性肿瘤之一。先前的研究表明， Smad4作为关键的调节因子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极其有限。本研究的目的是探讨 Smad4 调节 HO-8910 和 SKOV3 细胞活力和自噬的机制。我们观察到卵巢癌组织和细胞系中Smad4基因表达下调， Smad4过表达导致 HO-8910 和 SKOV3 细胞（卵巢癌细胞）增殖减少和自噬增加。我们还发现Smad4过表达可诱导卵巢癌细胞凋亡。免疫共沉淀分析还表明，Smad4 与 PI3K 的 P85 亚基相互作用，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进展的生物学机制，这可能会带来新的卵巢癌治疗策略。

 影响报告

本研究探讨了Smad4对卵巢癌（OC）细胞活力的影响和机制，并证明Smad4在OC中作为肿瘤抑制因子，这可能有助于理解OC发生和进展的分子机制。 OC 标本中 Smad4 表达降低，但 OC 细胞系中 Smad4 恢复通过增加自噬和凋亡而损害 OC 细胞的存活和活力。进一步研究表明，Smad4 与 PI3K 的 P85 亚基相互作用，导致 PI3K/mTOR 通路失活。因此，Smad4 由于其对 OC 癌变的调节作用，可被视为癌症治疗的靶点。