Retinol dehydrogenase 10 contributes to cancer stemness and intracellular carbohydrate storage in ovarian clear cell carcinomas.

IF 1.9 4区医学 Q3 ONCOLOGY Cancer Biomarkers Pub Date : 2022-01-01 DOI:10.3233/CBM-210435

Atsushi Murakami, Tsukuru Amano, Fumi Yoshino, Hiroko Kita, Suzuko Moritani, Takashi Murakami, Tokuhiro Chano

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Abstract

Background: Ovarian clear cell carcinomas (OCCCs) have been recurrent and refractory among the present treatments, so novel therapeutics are urgently needed.

Objective: The present study accumulates the proof of concept to examine the feasibility of RDH10 as a therapeutic target for treating OCCCs.

Methods: Immunohistochemically, RDH10 expression was evaluated in 111 primary epithelial ovarian cancers, including 55 OCCCs, 31 ovarian endometrioid carcinomas and 25 ovarian serous carcinomas. The spherogenecity provoked by RDH10 was evaluated in OCCC cells. To analyze whether RDH10 promotes carbohydrate storage via the vitamin A-gluconeogenesis pathway, phosphoenolpyruvate carboxykinase 1 (PCK1) protein levels and intracellular carbohydrate content were measured in response to modified RDH10 expression.

Results: Abundant RDH10 was expressed specifically in OCCCs. RDH10 promoted spherogenecity and intracellular carbohydrate storage via modulation of PCK1 expression in OCCC cells.

Conclusions: In the present study, abundant RDH10 contributed to cancer cell stemness and intracellular carbohydrate storage in OCCCs. RDH10 is a potentially, new therapeutic candidate for treating OCCC cases.

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视黄醇脱氢酶10参与卵巢透明细胞癌的癌变和细胞内碳水化合物储存。

背景：卵巢透明细胞癌（OCCCs）在目前的治疗中具有复发性和难治性，因此迫切需要新的治疗方法。目的：研究RDH10作为occc治疗靶点的可行性。方法：采用免疫组化方法检测111例原发性上皮性卵巢癌中RDH10的表达，包括55例occc、31例子宫内膜样癌和25例浆液性癌。在OCCC细胞中观察RDH10引起的球状性。为了分析RDH10是否通过维生素a -糖异生途径促进碳水化合物储存，我们检测了磷酸化烯醇丙酮酸羧激酶1 （phosphoenolpyruvate carboxykinase 1, PCK1）蛋白水平和细胞内碳水化合物含量对修饰RDH10表达的响应。结果：RDH10在occc中特异表达。RDH10通过调节OCCC细胞的PCK1表达促进细胞内碳水化合物的储存。结论：在本研究中，丰富的RDH10有助于occc细胞的干细胞性和细胞内碳水化合物的储存。RDH10是一种潜在的治疗OCCC病例的新候选药物。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Cancer Biomarkers ONCOLOGY-

CiteScore

5.20

自引率

3.20%

发文量

195

审稿时长

3 months

期刊介绍： Concentrating on molecular biomarkers in cancer research, Cancer Biomarkers publishes original research findings (and reviews solicited by the editor) on the subject of the identification of markers associated with the disease processes whether or not they are an integral part of the pathological lesion. The disease markers may include, but are not limited to, genomic, epigenomic, proteomics, cellular and morphologic, and genetic factors predisposing to the disease or indicating the occurrence of the disease. Manuscripts on these factors or biomarkers, either in altered forms, abnormal concentrations or with abnormal tissue distribution leading to disease causation will be accepted.