Luo Jianjun, Yi Ting, Wang Yong, Song Wei, Gao Zhiyong, Wang Jiansong, Li Yukun
Department of Urology, Hunan Provincial People's Hospital, The First Affiliated Hospital of Hunan Normal University, Changsha, 410005, Hunan Province, China.
Department of Assisted Reproductive Centre, Zhuzhou Central Hospital, Xiangya Hospital Zhuzhou Central South University, Central South University, Zhuzhou, Hunan, China.
Sci Rep. 2025 Feb 10;15(1):4902. doi: 10.1038/s41598-024-82400-z.
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.
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中的表达及预后情况。免疫组化染色显示了ESM1在KIRC样本中的蛋白表达。通过MTT、EdU、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其旁分泌功能在KIRC血管生成中的作用。通过蛋白质印迹法(WB)和功能实验进一步阐明了ESM1的下游分子机制。ESM1在KIRC中显著升高,具有预后意义。敲低ESM1可抑制KIRC细胞的侵袭能力和活力。在KIRC细胞条件培养基中,ESM1的旁分泌增强了人脐静脉内皮细胞(HUVECs)的增殖和迁移以形成血管。敲低ESM1可诱导Akt/mTOR和Ras通路失活,从而减弱KIRC中的增殖、迁移、侵袭和血管生成。ESM1在KIRC的肿瘤微环境(TME)中起关键作用,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患者潜在的治疗靶点。