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下调 miR-10b-5p 促进子宫平滑肌肉瘤细胞的增殖:基于 microRNA 测序的方法。

Downregulation of miR‑10b‑5p facilitates the proliferation of uterine leiomyosarcoma cells: A microRNA sequencing‑based approach.

机构信息

Department of Obstetrics and Gynecology, Nagoya University Graduate School of Medicine, Nagoya, Aichi 466‑8550, Japan.

Bell Research Center, Department of Obstetrics and Gynecology Collaborative Research, Nagoya University Graduate School of Medicine, Nagoya, Aichi 466‑8550, Japan.

出版信息

Oncol Rep. 2023 May;49(5). doi: 10.3892/or.2023.8523. Epub 2023 Mar 17.

Abstract

Uterine leiomyosarcoma (ULMS) is one of the most aggressive gynecological malignancies. In addition, the molecular background of ULMS has not been fully elucidated due to its low incidence. Therefore, no effective treatment strategies have been established based on its molecular background. The present study aimed to investigate the roles of microRNAs (miRNAs/miRs) in the development of ULMS. Comprehensive miRNA sequencing was performed using six ULMS and three myoma samples, and revealed 53 and 11 significantly upregulated and downregulated miRNAs, respectively. One of the most abundant miRNAs in myoma samples was miR‑10b‑5p. The mean normalized read count of miR‑10b‑5p was 93,650 reads in myoma, but only 27,903 reads in ULMS. Subsequently, to investigate the roles of miR‑10b‑5p, gain‑of‑function analysis was performed using SK‑UT‑1 and SK‑LMS‑1 cell lines. The overexpression of miR‑10b‑5p suppressed cell proliferation and reduced the number of colonies. Moreover, miR‑10b‑5p increased the number of cells in the G phase. In conclusion, tumor‑suppressive miR‑10b‑5p was significantly downregulated in ULMS compared with in myoma; thus, miR‑10b‑5p may serve a specific role in sarcoma progression.

摘要

子宫平滑肌肉瘤(ULMS)是最具侵袭性的妇科恶性肿瘤之一。此外,由于其发病率低,ULMS 的分子背景尚未完全阐明。因此,尚未基于其分子背景建立有效的治疗策略。本研究旨在探讨 microRNAs(miRNAs/miRs)在 ULMS 发展中的作用。使用六个 ULMS 和三个肌瘤样本进行了全面的 miRNA 测序,分别发现了 53 个和 11 个显著上调和下调的 miRNA。在肌瘤样本中最丰富的 miRNA 之一是 miR-10b-5p。miR-10b-5p 的平均归一化读数在肌瘤中为 93650 个读数,而在 ULMS 中仅为 27903 个读数。随后,为了研究 miR-10b-5p 的作用,使用 SK-UT-1 和 SK-LMS-1 细胞系进行了功能获得分析。miR-10b-5p 的过表达抑制了细胞增殖并减少了集落的数量。此外,miR-10b-5p 增加了 G 期细胞的数量。总之,与肌瘤相比,ULMS 中肿瘤抑制性 miR-10b-5p 明显下调;因此,miR-10b-5p 可能在肉瘤进展中发挥特定作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6000/10073409/352472d92271/or-49-05-08523-g00.jpg

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