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环状 RNA hsa_circ_0072309 通过激活 PPARγ/PTEN 信号抑制 PI3K/AKT 信号来抑制胃癌细胞的增殖、侵袭和迁移。

Circular RNA hsa_circ_0072309 inhibits the proliferation, invasion and migration of gastric cancer cells via inhibition of PI3K/AKT signaling by activating PPARγ/PTEN signaling.

机构信息

Department of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215000, P.R. China.

The Stem Cell and Biomedical Material Key Laboratory of Jiangsu Province (The State Key Laboratory Incubation Base), Soochow University, Suzhou, Jiangsu 215000, P.R. China.

出版信息

Mol Med Rep. 2021 May;23(5). doi: 10.3892/mmr.2021.11988. Epub 2021 Mar 24.

Abstract

Gastric cancer (GC) is a common malignant tumor in the digestive system, which presents without specific symptoms. Circular RNAs (circRNAs) play important roles in tumor progression and cellular functions; however, the relationship between GC and hsa_circ_0072309 remains unclear. The aim of the present study was to investigate the molecular mechanisms of hsa_circ_0072309 and the role that hsa_circ_0072309 plays in proliferation, invasion and migration of GC cells. The expression of hsa_circ_0072309 was evaluated using reverse transcription‑quantitative PCR. A series of functional experiments were performed to study the role that hsa_circ_0072309 has in survival and metastasis of GC cells. In the present study, hsa_circ_0072309 was downregulated in GC cell lines and its overexpression inhibited the proliferation, migration and invasion of GC cells. In addition, hsa_circ_0072309 overexpression induced activation of the peroxisome proliferator‑activated receptor γ (PPARγ)/PTEN pathway and inhibition of PI3K/AKT signaling. Moreover, pioglitazone, a PPARγ agonist, strengthened the effects of abundant hsa_circ_0072309 on the proliferative, migratory and invasive capabilities of GC cells, while GW9662, a PPARγ antagonist, abolished the effects of hsa_circ_0072309 overexpression on cell proliferation, migration and invasion. The present findings suggested that hsa_circ_0072309 inhibited proliferation, invasion and migration of gastric cancer cells via the inhibition of PI3K/AKT signaling by activating the PPARγ/PTEN signaling pathway. Targeting hsa_circ_0072309 may be an innovative therapeutic strategy for the treatment of GC.

摘要

胃癌(GC)是消化系统常见的恶性肿瘤,其发病无特异性症状。环状 RNA(circRNA)在肿瘤进展和细胞功能中发挥重要作用;然而,GC 与 hsa_circ_0072309 之间的关系尚不清楚。本研究旨在探讨 hsa_circ_0072309 的分子机制及其在 GC 细胞增殖、侵袭和迁移中的作用。采用逆转录-定量 PCR 检测 hsa_circ_0072309 的表达。通过一系列功能实验研究 hsa_circ_0072309 在 GC 细胞存活和转移中的作用。在本研究中,hsa_circ_0072309 在 GC 细胞系中下调,其过表达抑制 GC 细胞的增殖、迁移和侵袭。此外,hsa_circ_0072309 过表达诱导过氧化物酶体增殖物激活受体 γ(PPARγ)/PTEN 通路激活和 PI3K/AKT 信号通路抑制。此外,PPARγ 激动剂吡格列酮增强了丰富的 hsa_circ_0072309 对 GC 细胞增殖、迁移和侵袭能力的影响,而 PPARγ 拮抗剂 GW9662 则消除了 hsa_circ_0072309 过表达对细胞增殖、迁移和侵袭的影响。本研究结果表明,hsa_circ_0072309 通过激活 PPARγ/PTEN 信号通路抑制 PI3K/AKT 信号通路抑制胃癌细胞的增殖、侵袭和迁移。针对 hsa_circ_0072309 可能是治疗 GC 的一种创新治疗策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/eceb/7974328/8ff64a16fb9e/mmr-23-05-11988-g00.jpg

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