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紫杉醇热疗通过 miR-183-5p/PPP2CA/AKT/GSK3β/β-catenin 轴抑制胃癌迁移。

Paclitaxel hyperthermia suppresses gastric cancer migration through MiR-183-5p/PPP2CA/AKT/GSK3β/β-catenin axis.

机构信息

Department of Anus and Intestine Surgery, The First People's Hospital of Foshan, Foshan, 528000, China.

Medical Affair Department, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510000, China.

出版信息

J Cancer Res Clin Oncol. 2024 Sep 9;150(9):416. doi: 10.1007/s00432-024-05923-y.

Abstract

BACKGROUND

Gastric cancer (GC), a prevalent malignant tumor which is a leading cause of death from malignancy around the world. Peritoneal metastasis accounts for the major cause of mortality in patients with GC. Despite hyperthermia intraperitoneal chemotherapy (HIPEC) improves the therapeutic effect of GC, it's equivocal about the mechanism under HIPEC.

METHODS

MiR-183-5p expression was sifted from miRNA chip and detected in both GC patients and cell lines by qRT-PCR. Gene interference and rescue experiments were performed to identified biological function in vitro and vivo. Next, we affirmed PPP2CA as targeted of miR-183-5p by dual luciferase reporter assay. Finally, the potential relationship between HIPEC and miR-183-5p was explored.

RESULTS

MiR-183-5p is up-regulated in GC and associated with advanced stage and poor prognosis. MiR-183-5p accelerate GC migration in vitro which is influenced by miR-183-5p/PPP2CA/AKT/GSK3β/β-catenin Axis. HIPEC exerts migration inhibition via attenuating miR-183-5p expression.

CONCLUSION

MiR-183-5p can be used as a potential HIPEC biomarker in patients with CC.

摘要

背景

胃癌(GC)是一种常见的恶性肿瘤,是全球恶性肿瘤死亡的主要原因。腹膜转移是 GC 患者死亡的主要原因。尽管腹腔内热灌注化疗(HIPEC)提高了 GC 的治疗效果,但 HIPEC 的机制仍存在争议。

方法

通过 miRNA 芯片筛选出 miR-183-5p 的表达,并通过 qRT-PCR 在 GC 患者和细胞系中进行检测。通过基因干扰和挽救实验,在体外和体内鉴定了其生物学功能。接下来,我们通过双荧光素酶报告基因实验证实 PPP2CA 是 miR-183-5p 的靶基因。最后,探讨了 HIPEC 与 miR-183-5p 之间的潜在关系。

结果

miR-183-5p 在 GC 中上调,与晚期和预后不良相关。miR-183-5p 促进 GC 体外迁移,受 miR-183-5p/PPP2CA/AKT/GSK3β/β-catenin 轴的影响。HIPEC 通过降低 miR-183-5p 的表达来发挥迁移抑制作用。

结论

miR-183-5p 可作为 CC 患者 HIPEC 的潜在生物标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4b97/11793590/4b8e29560793/432_2024_5923_Fig1_HTML.jpg

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