MKRN1/2通过调控p53的表达在肾透明细胞癌中起抑瘤作用。

IF 2.2 4区 医学 Q3 ONCOLOGY
Yun Yang, Yanyan Luo, Shuting Huang, Yonghui Tao, Chuanyin Li, Chengcheng Wang
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引用次数: 0

摘要

背景:肾透明细胞癌(KIRC)属于肾细胞癌,是一种预后差、死亡率高、侵袭性强的恶性肿瘤。MKRN家族包括MKRN1、MKRN2和MKRN3三个成员,这三个成员与癌症密切相关,已经参与了许多研究。目的:探讨MKRN家族在KIRC中的作用。方法:采用UALCAN数据库分析mkrn的表达情况,采用GEPIA2和Kaplan-Meier Plotter数据库进行预后分析,并采用GEPIA2进行相关性分析。采用CCK-8法和集落形成法检测细胞增殖,采用创面愈合法检测细胞迁移,采用流式细胞术检测细胞周期,采用GST下拉法和共免疫沉淀法检测蛋白相互作用,采用免疫印迹法或定量PCR (qPCR)检测MKRNs、p53等蛋白的表达。结果:与相应的正常组织相比,MKRN1和MKRN2在KIRC样本中表达较低,高水平MKRN1和MKRN2的KIRC患者总体生存率(OS)和无病生存率(DFS)更高。MKRN1和MKRN2过表达通过阻滞细胞周期抑制人KIRC细胞的增殖,但对细胞迁移影响不大。MKRN1和MKRN2的表达是相关的,且MKRN1与MKRN2直接相互作用。此外,MKRN1和MKRN2与TP53在KIRC肿瘤中的表达密切相关,并在蛋白和mRNA水平上促进p53的表达。结论:我们的研究提示MKRN1和MKRN2在KIRC中发挥抑瘤作用,是KIRC治疗的有希望的治疗靶点。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
MKRN1/2 serve as tumor suppressors in renal clear cell carcinoma by regulating the expression of p53.

Background: Kidney renal clear cell carcinoma (KIRC) belongs to renal cell carcinoma which is a very aggressive malignant tumor with poor prognosis and high mortality. The MKRN family includes three members MKRN1, MKRN2 and MKRN3, which are closely related to cancers, and have been involved in many studies.

Objective: This study aimed to explore the roles of MKRN family in KIRC.

Methods: The expression of MKRNs was analyzed using the UALCAN database, prognostic analysis was performed with the GEPIA2 and Kaplan-Meier Plotter database, and correlation analysis was assessed by GEPIA2. The CCK-8 and colony formation assay were performed to detect cell proliferation, wound healing assays were performed to detect cell migration, cell cycles were detected by flow cytometry analysis, GST pull-down and co-immunoprecipitation assays were performed to detect the interaction of proteins, and the expression of MKRNs, p53 and other proteins were detect by immunoblotting analysis or quantitative PCR (qPCR).

Results: MKRN1 and MKRN2 were lowly expressed in KIRC samples compared to the corresponding normal tissues, and KIRC patients with high levels of MKRN1 and MKRN2 showed higher overall survival (OS) and disease free survival (DFS) rates. The overexpression of MKRN1 and MKRN2 inhibited the proliferation of human KIRC cells by arresting the cell cycles, but shows little effect on cells migration. The expression of MKRN1 and MKRN2 are correlated, and MKRN1 directly interacts with MKRN2. Moreover, both MKRN1 and MKRN2 were closely correlated with the expression of TP53 in KIRC tumor, and promoted the expression of p53 both at protein and mRNA levels.

Conclusions: Our study suggests that MKRN1 and MKRN2 serve as tumor suppressors in KIRC, and act as promising therapeutic targets for KIRC treatment.

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来源期刊
Cancer Biomarkers
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.
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