Transcription factor E2F7 activates PKMYT1 to partially suppress adriamycin sensitivity in gastric cancer through the MAPK signaling pathway.

IF 1.4 4区医学 Q2 Medicine Revista De Investigacion Clinica-Clinical and Translational Investigation Pub Date : 2024-03-01 DOI:10.24875/RIC.23000180

Xianjin Yang, Jie Zeng, Changhong Jiang, Yi Zhang, Xu Zhang

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Abstract

Background: Adriamycin resistance remains an obstacle to gastric cancer chemotherapy treatment. Objective: The objective of this study was to study the role and mechanism of transcription factor E2F7 in sensitivity to ADM chemotherapeutic agents in gastric cancer.

Methods: Cell viability and cell sensitivity were assessed by CCK-8 and IC50 values of ADM were calculated. The impact of ADM on cellular proliferative capacity was assessed through colony formation assay. The binding relationship between E2F7 and PKMYT1 was then verified by dual luciferase assay and chromatin immunoprecipitation assay. ERK1/ERK2 and p-ERK1/p-ERK2 protein expression levels were detected by western blot.

Results: In both gastric cancer tissue and ADM-resistant cells, a conspicuous upregulation of E2F7 and PKMYT1 was observed. Upregulated PKMYT1 was notably enriched in the MAPK signaling pathway. Enhanced levels of E2F7 were shown to not only drive gastric cancer cell proliferation but also engender a reduction in the sensitivity of these cells to ADM. Furthermore, PKMYT1 emerged as a downstream target of E2F7. Activation of E2F7 culminated in the transcriptional upregulation of PKMYT1, and silencing E2F7 reversed the inhibitory impact of PKMYT1 overexpression on ADM sensitivity in gastric cancer cells.

Conclusion: E2F7/PKMYT1 axis might promote the proliferation and partially inhibit ADM sensitivity of gastric cancer cells by activating the MAPK pathway.

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转录因子E2F7激活PKMYT1，通过MAPK信号通路部分抑制胃癌对阿霉素的敏感性

背景：阿霉素耐药性仍是胃癌化疗的障碍之一。研究目的本研究旨在探讨转录因子 E2F7 在胃癌患者对 ADM 化疗药物敏感性中的作用和机制：方法：用CCK-8评估细胞活力和细胞敏感性，并计算ADM的IC50值。通过集落形成试验评估ADM对细胞增殖能力的影响。然后通过双荧光素酶试验和染色质免疫沉淀试验验证了E2F7和PKMYT1之间的结合关系。ERK1/ERK2和p-ERK1/p-ERK2蛋白的表达水平由Western印迹法检测：结果：在胃癌组织和抗 ADM 细胞中，均观察到 E2F7 和 PKMYT1 的明显上调。上调的 PKMYT1 在 MAPK 信号通路中明显富集。研究表明，E2F7水平的提高不仅能促进胃癌细胞增殖，还能降低这些细胞对ADM的敏感性。此外，PKMYT1 成为了 E2F7 的下游靶点。E2F7的激活最终导致PKMYT1的转录上调，而沉默E2F7可逆转PKMYT1过表达对胃癌细胞ADM敏感性的抑制作用：结论：E2F7/PKMYT1轴可通过激活MAPK通路促进胃癌细胞的增殖并部分抑制其对ADM的敏感性。

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

Revista De Investigacion Clinica-Clinical and Translational Investigation 医学-医学：内科

CiteScore

3.00

自引率

0.00%

发文量

审稿时长

>12 weeks

期刊介绍： The Revista de Investigación Clínica – Clinical and Translational Investigation (RIC-C&TI), publishes original clinical and biomedical research of interest to physicians in internal medicine, surgery, and any of their specialties. The Revista de Investigación Clínica – Clinical and Translational Investigation is the official journal of the National Institutes of Health of Mexico, which comprises a group of Institutes and High Specialty Hospitals belonging to the Ministery of Health. The journal is published both on-line and in printed version, appears bimonthly and publishes peer-reviewed original research articles as well as brief and in-depth reviews. All articles published are open access and can be immediately and permanently free for everyone to read and download. The journal accepts clinical and molecular research articles, short reports and reviews. Types of manuscripts: – Brief Communications – Research Letters – Original Articles – Brief Reviews – In-depth Reviews – Perspectives – Letters to the Editor