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PIEZO2 通过 SLIT2/ROBO1/VEGFC 通路促进结肠癌细胞的增殖和转移。

PIEZO2 promotes cell proliferation and metastasis in colon carcinoma through the SLIT2/ROBO1/VEGFC pathway.

机构信息

People's Hospital, Lianyungang Clinical College of Bengbu Medical College, China.

出版信息

Adv Clin Exp Med. 2023 Jul;32(7):763-776. doi: 10.17219/acem/157515.

Abstract

BACKGROUND

The PIEZO2 may be involved in the occurrence and development of tumors.

OBJECTIVES

To explore the potential mechanism and effect of PIEZO2 on colon cancer.

MATERIAL AND METHODS

We assessed the expression and prognostic role of PIEZO2 in patients with colon cancer. The role of PIEZO2 in SW480 cell proliferation, migration and invasion in vitro was investigated using cell counting kit-8 (CCK-8), wound healing, and transwell and cell invasion assays, respectively. The effect of PIEZO2 on SW480 cells in vivo was also explored. The potential mechanisms of PIEZO2 in SW480 cells were detected using quantitative reverse-transcription polymerase chain reaction (qRT-PCR) and western blot.

RESULTS

The PIEZO2 was significantly increased in colon cancer tissues and the PIEZO2 high expression group was associated with a lower overall survival (OS) rate. Furthermore, PIEZO2 knockdown weakened the proliferation, migration and invasion of SW480 cells. The PIEZO2 knockdown was related to a lower expression of SLIT2, ROBO1, HIF-1α, and VEGFC. Finally, the tumors in control SW480 cells grew faster and larger than those in mice inoculated with si-PIEZO2 SW480 cells. Moreover, the si-PIEZO2 SW480 cell group showed a reduced expression of Ki67 and VEGFC and, at the same time, a significantly higher apoptosis index of tumor cells compared to the control group. The expression of PIEZO2 was higher in cancer-associated fibroblasts (CAFs) of colon cancer.

CONCLUSIONS

The PIEZO2 was increased in colon cancer tissues and was an unfavorable gene in patients with colon cancer, promoting colon cell proliferation, migration and invasion through the SLIT2/ROBO1/VEGFC pathway.

摘要

背景

PIEZO2 可能参与肿瘤的发生和发展。

目的

探索 PIEZO2 对结肠癌的潜在作用机制。

材料和方法

我们评估了 PIEZO2 在结肠癌患者中的表达和预后作用。通过细胞计数试剂盒-8 (CCK-8)、划痕愈合、Transwell 和细胞侵袭实验分别研究了 PIEZO2 对 SW480 细胞体外增殖、迁移和侵袭的作用。还探索了 PIEZO2 对 SW480 细胞体内的影响。通过定量逆转录聚合酶链反应 (qRT-PCR) 和 Western blot 检测 PIEZO2 在 SW480 细胞中的潜在作用机制。

结果

PIEZO2 在结肠癌组织中显著增加,PIEZO2 高表达组的总生存率 (OS) 较低。此外,PIEZO2 敲低削弱了 SW480 细胞的增殖、迁移和侵袭。PIEZO2 敲低与 SLIT2、ROBO1、HIF-1α 和 VEGFC 的表达降低有关。最后,与接种 si-PIEZO2 SW480 细胞的小鼠相比,对照 SW480 细胞的肿瘤生长更快、更大。此外,与对照组相比,si-PIEZO2 SW480 细胞组肿瘤细胞的 Ki67 和 VEGFC 表达减少,同时细胞凋亡指数显著升高。PIEZO2 在结肠癌相关成纤维细胞 (CAFs) 中的表达较高。

结论

PIEZO2 在结肠癌组织中增加,是结肠癌患者的不利基因,通过 SLIT2/ROBO1/VEGFC 通路促进结肠细胞增殖、迁移和侵袭。

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