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HOXA-AS3 通过上皮-间充质转化途径诱导上皮性卵巢癌的肿瘤进展。

HOXA‑AS3 induces tumor progression through the epithelial‑mesenchymal transition pathway in epithelial ovarian cancer.

机构信息

Department of Obstetrics and Gynecology, Center for Digital Health, Yongin Severance Hospital, Yonsei University College of Medicine, Yongin, Gyeonggi‑do 16995, Republic of Korea.

Department of Obstetrics and Gynecology, Bucheon St. Mary's Hospital, College of Medicine, Catholic University of Korea, Bucheon, Gyeonggi‑do 14647, Republic of Korea.

出版信息

Oncol Rep. 2023 Mar;49(3). doi: 10.3892/or.2023.8501. Epub 2023 Feb 17.

Abstract

HOXA cluster antisense RNA 3 (HOXA‑AS3) is considered to be involved in several malignancies, however, its biological function in the progression of epithelial ovarian cancer (EOC) remains unclear. The present study compared the expression of HOXA‑AS3 in ovarian cancer and normal ovarian tissues and analyzed the association between the expression of HOXA‑AS3 and the survival outcomes of patients with ovarian cancer. RNA interference was used to suppress HOXA‑AS3 expression in ovarian cancer cell lines in order to demonstrate the function of HOXA‑AS3 in ovarian cancer progression. The associations between HOXA‑AS3 and epithelial‑mesenchymal transition (EMT) markers were explored to verify the mechanism of action of HOXA‑AS3 in ovarian cancer. The results of the present study revealed that ovarian cancer tissues exhibited higher HOXA‑AS3 expression than normal ovarian tissues. Clinical data indicated that HOXA‑AS3 was a significant predictor of progression‑free survival and overall survival. Patients with high HOXA‑AS3 expression had a poorer prognosis than patients with low HOXA‑AS3 expression. experiments using HOXA‑AS3‑knockdown ovarian cancer cell lines demonstrated that HOXA‑AS3 knockdown inhibited cell proliferation and migration. HOXA‑AS3 was a potent inducer and modulator of the expression of EMT pathway‑related markers and interacted with both the mRNA and protein forms of HOXA3. Collectively, the findings of the present study demonstrated that HOXA‑AS3 expression is associated with ovarian cancer progression and thus, may be employed as a prognostic marker and therapeutic target in EOC.

摘要

HOXA 簇反义 RNA3(HOXA-AS3)被认为参与多种恶性肿瘤,但它在卵巢上皮性癌(EOC)进展中的生物学功能尚不清楚。本研究比较了 HOXA-AS3 在卵巢癌和正常卵巢组织中的表达,并分析了 HOXA-AS3 的表达与卵巢癌患者生存结局之间的关系。采用 RNA 干扰抑制卵巢癌细胞系中 HOXA-AS3 的表达,以证实 HOXA-AS3 在卵巢癌进展中的作用。探讨了 HOXA-AS3 与上皮-间充质转化(EMT)标志物之间的关联,以验证 HOXA-AS3 在卵巢癌中的作用机制。本研究结果表明,卵巢癌组织中 HOXA-AS3 的表达高于正常卵巢组织。临床资料表明,HOXA-AS3 是无进展生存期和总生存期的显著预测因子。HOXA-AS3 高表达的患者预后较 HOXA-AS3 低表达的患者差。使用 HOXA-AS3 敲低卵巢癌细胞系的实验表明,HOXA-AS3 敲低抑制了细胞增殖和迁移。HOXA-AS3 是 EMT 通路相关标志物表达的有力诱导剂和调节剂,与 HOXA3 的 mRNA 和蛋白形式相互作用。综上所述,本研究结果表明,HOXA-AS3 的表达与卵巢癌的进展相关,因此,可作为 EOC 的预后标志物和治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fa2f/9944947/dbac549c25b8/or-49-03-08501-g00.jpg

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