Ovarian cancer has ranked as one of the leading causes of female morbidity and mortality around the world, which affects ∼239,000 patients and causes 152,000 deaths every year. Chemotherapeutic resistance of ovarian cancer remains a devastating actuality in clinic. The aberrant upregulation of long non-coding RNA succinate dehydrogenase complex flavoprotein subunit A pseudogene 1 (lncRNA SDHAP1) in the Paclitaxel (PTX)-resistant ovarian cancer cell lines has been reported. However, studies focussed on SDHAP1 in its regulatory function of chemotherapeutic resistance in ovarian cancer are limited, and the detailed mechanisms remain unclear. In this study, we demonstrated that SDHAP1 was upregulated in PTX-resistant SKOV3 and Hey-8 ovarian cancer cell lines while the level of miR-4465 was downregulated. Knocking-down SDHAP1 induced re-acquirement of chemo-sensitivity to PTX in ovarian cancer cells in vitro. Mechanically, SDHAP1 upregulated the expression of EIF4G2 by sponging miR-4465 and thus facilitated the PTX-induced apoptosis in ovarian cancer cells. The regulation network involving SDHAP1, miR-4465 and EIF4G2 could be a potential therapy target for the PTX-resistant ovarian cancer.

中文翻译：

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LncRNA SDHAP1通过miR-4465调节EIF4G2表达，从而赋予卵巢癌紫杉醇耐药性。

卵巢癌被认为是全球女性发病率和死亡率的主要原因之一，每年影响约239,000名患者，并导致152,000例死亡。卵巢癌的化学治疗抗性在临床上仍然是毁灭性的现实。长期的非编码RNA琥珀酸脱氢酶复合物黄素蛋白亚基A假基因1（lncRNA SDHAP1）在紫杉醇（PTX）抗性卵巢癌细胞系中的异常上调已有报道。然而，针对SDHAP1的研究对卵巢癌化疗耐药性的调节功能有限，其详细机制仍不清楚。在这项研究中，我们证明SDHAP1在耐PTX的SKOV3和Hey-8卵巢癌细胞系中上调，而miR-4465的水平下调。体外。机械上，SDHAP1通过使miR-4465变海绵状上调EIF4G2的表达，从而促进PTX诱导的卵巢癌细胞凋亡。涉及SDHAP1，miR-4465和EIF4G2的调控网络可能是对PTX耐药的卵巢癌的潜在治疗靶标。