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微小RNA-362-3p通过抑制低密度脂蛋白受体相关蛋白8来抑制卵巢癌。

miR-362-3p suppresses ovarian cancer by inhibiting LRP8.

作者信息

Li Chun, Yang Yi, Wang Huimin, Song Yu, Huang Huan

机构信息

Department of Obstetrics and Gynecology, Wuhan Third Hospital, No. 216 Guanshan Avenue, Hongshan, Wuhan, Hubei 430060, China.

Department of Obstetrics and Gynecology, Wuhan Third Hospital, No. 216 Guanshan Avenue, Hongshan, Wuhan, Hubei 430060, China.

出版信息

Transl Oncol. 2022 Jan;15(1):101284. doi: 10.1016/j.tranon.2021.101284. Epub 2021 Nov 26.

Abstract

BACKGROUND

Ovarian cancer is one of the most common female cancers, with a high incidence worldwide. Aberrant expression of low-density lipoprotein (LDL) receptor-related protein 8 (LRP8) and microRNA (miR)-362-3p is involved in the pathogenesis of different cancers.

METHODS

We aimed to elucidate the underlying mechanism of the miR-362-3p-LRP8 axis in ovarian cancer. Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was used to examine miR-362-3p and LRP8 expression in ovarian cancer tissues and cells. The luciferase assay was used to determine the relationship between miR-362-3p and LRP8. The function of overexpression of miR-362-3p and LRP8 was determined by assessing the cell viability using the cell counting kit 8 (CCK-8) assay, proliferation using 5'‑bromo-2'-deoxyuridine (BrdU) assay, migration using wound healing assay, invasion using transwell assay, and the protein expression levels of matrix metalloproteinase (MMP)-2, MMP9, and integrin α5 or β1 using western blotting assays in ovarian cancer cells.

RESULTS

miR-362-3p expression levels were decreased in ovarian cancer tissues and cells and negatively correlated with LRP8 levels. Overexpression of miR-362-3p dramatically repressed cell growth. Furthermore, overexpression of LRP8 significantly facilitated the proliferation, migration, and invasion of ovarian cancer cells, which counteracted the inhibitory effect of miR-362-3p on ovarian cancer cell growth.

CONCLUSIONS

We reported that miR-362-3p hampered cell growth by repressing LRP8 expression in ovarian cancer cells. Our results provide new insights into ovarian cancer, involving both miR-362-3p and LRP8, which can be used as potential biomarkers for the treatment of ovarian cancer.

摘要

背景

卵巢癌是最常见的女性癌症之一,在全球范围内发病率很高。低密度脂蛋白(LDL)受体相关蛋白8(LRP8)和微小RNA(miR)-362-3p的异常表达参与了不同癌症的发病机制。

方法

我们旨在阐明miR-362-3p-LRP8轴在卵巢癌中的潜在机制。采用定量逆转录-聚合酶链反应(qRT-PCR)检测卵巢癌组织和细胞中miR-362-3p和LRP8的表达。荧光素酶报告基因检测用于确定miR-362-3p与LRP8之间的关系。通过细胞计数试剂盒8(CCK-8)检测评估细胞活力、5'-溴-2'-脱氧尿苷(BrdU)检测评估增殖、伤口愈合检测评估迁移、Transwell检测评估侵袭,以及蛋白质印迹检测评估卵巢癌细胞中基质金属蛋白酶(MMP)-2、MMP9和整合素α5或β1的蛋白质表达水平,来确定miR-362-3p和LRP8过表达的功能。

结果

卵巢癌组织和细胞中miR-362-3p表达水平降低,且与LRP8水平呈负相关。miR-362-3p过表达显著抑制细胞生长。此外,LRP8过表达显著促进卵巢癌细胞的增殖、迁移和侵袭,抵消了miR-362-3p对卵巢癌细胞生长的抑制作用。

结论

我们报道miR-362-3p通过抑制卵巢癌细胞中LRP8的表达来阻碍细胞生长。我们的结果为卵巢癌提供了新的见解,涉及miR-362-3p和LRP8,它们可作为治疗卵巢癌的潜在生物标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4129/8636862/4f43ca14b79b/gr1.jpg

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