ESM1通过Akt/mTOR和Ras通路促进肾透明细胞癌的增殖、侵袭和血管生成。

IF 3.9 2区 综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES
Jianjun Luo, Ting Yi, Yong Wang, Wei Song, Zhiyong Gao, Jiansong Wang, Yukun Li
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引用次数: 0

摘要

最常见的肾癌类型是肾透明细胞癌(KIRC)。ESM1是一种分泌蛋白,参与脂质和葡萄糖代谢,但其在血管生成中的作用在不同疾病中存在矛盾,尤其是在KIRC中。生物信息学分析证实了ESM1在KIRC中的表达和预后。IHC染色显示ESM1在KIRC样本中的蛋白表达。通过 MTT、EdU 和 transwell 分析检测了 ESM1 在 KIRC 增殖和迁移中的作用。通过功能实验检测了ESM1在KIRC血管生成中的旁分泌功能。通过WB和功能实验进一步阐明了ESM1的下游分子机制。ESM1在KIRC中明显升高,具有预后意义。敲除ESM1可抑制KIRC细胞的侵袭能力和存活率。ESM1的旁分泌作用增强了KIRC细胞条件培养基中HUVECs的增殖和向格式管的迁移。敲除ESM1会导致Akt/mTOR和Ras通路失活,从而抑制KIRC细胞的增殖、迁移、侵袭和血管生成。ESM1在KIRC的肿瘤微环境(TME)中起着关键作用,它通过激活Akt/mTOR和Ras通路促进增殖、迁移、侵袭和血管生成。它是 KIRC 患者的潜在治疗靶点。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
ESM1 promote proliferation, invasion and angiogenesis via Akt/mTOR and Ras pathway in kidney renal clear cell carcinoma.

The most common types of renal carcinoma is kidney renal clear cell carcinoma (KIRC). ESM1 is a secreted protein, which involved in, lipids and glucose metabolism, but their role in angiogenesis is contradictory in different disease, especially in KIRC. Bioinformatic analysis confirmed the ESM1 expression and prognosis in KIRC. IHC staining revealed protein expression of ESM1 in KIRC samples. The role of ESM1 in KIRC proliferation and migration were tested by MTT, EdU, transwell analysis. The role of its paracrine function in KIRC angiogenesis was tested by functional experiments. The downstream molecular mechanism of ESM1 were further elucidated by WB and functional experiments. ESM1 was significantly increased in KIRC with prognostic significance. ESM1 knockdown inhibited the invasiveness capability and viability of KIRC cell. The paracrine of ESM1 enhanced HUVECs proliferation and migration to format tube in KIRC cell conditional medium. ESM1 knockdown induced the inactivation of Akt/mTOR and Ras pathway to attenuate proliferation, migration, invasion and angiogenesis in KIRC. ESM1 was a key role in the tumor microenvironment (TME) of KIRC, which promoted the proliferation, migration, invasion, and angiogenesis by activating Akt/mTOR and Ras pathway. It is a potential therapeutic target for KIRC patients.

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来源期刊
Scientific Reports
Scientific Reports Natural Science Disciplines-
CiteScore
7.50
自引率
4.30%
发文量
19567
审稿时长
3.9 months
期刊介绍: We publish original research from all areas of the natural sciences, psychology, medicine and engineering. You can learn more about what we publish by browsing our specific scientific subject areas below or explore Scientific Reports by browsing all articles and collections. Scientific Reports has a 2-year impact factor: 4.380 (2021), and is the 6th most-cited journal in the world, with more than 540,000 citations in 2020 (Clarivate Analytics, 2021). •Engineering Engineering covers all aspects of engineering, technology, and applied science. It plays a crucial role in the development of technologies to address some of the world''s biggest challenges, helping to save lives and improve the way we live. •Physical sciences Physical sciences are those academic disciplines that aim to uncover the underlying laws of nature — often written in the language of mathematics. It is a collective term for areas of study including astronomy, chemistry, materials science and physics. •Earth and environmental sciences Earth and environmental sciences cover all aspects of Earth and planetary science and broadly encompass solid Earth processes, surface and atmospheric dynamics, Earth system history, climate and climate change, marine and freshwater systems, and ecology. It also considers the interactions between humans and these systems. •Biological sciences Biological sciences encompass all the divisions of natural sciences examining various aspects of vital processes. The concept includes anatomy, physiology, cell biology, biochemistry and biophysics, and covers all organisms from microorganisms, animals to plants. •Health sciences The health sciences study health, disease and healthcare. This field of study aims to develop knowledge, interventions and technology for use in healthcare to improve the treatment of patients.
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