Background

Our previous study showed that CXCL11 could play an immunomodulatory role. In this study, we investigated the regulator (miR-205–3p) of CXCL11 and the mechanism of miR-205–3p as a tumor suppressor gene in gastric cancer (GC).

Materials and methods

A target relationship between miR-205–3p and CXCL11 was revealed by using the bioinformatics method. This study detected the expressions of miR-205–3p and CXCL11 through qRT-PCR and Western blotting. Moreover, the expressions of Akt, PD-L1, p16, p21, and senescence-associated secretory phenotype (SASP) factor were determined. The effects of miR-205 on proliferation, invasion, and senescence of GC cells were assessed by using methods, such as transfection, Transwell assay, tablet cloning, flow cytometry, and senescence-associated beta-galactosidase (SA-β-gal) staining. Furthermore, the effects were verified using methods, like immunohistochemistry, flow cytometry and SA-β-gal in animal experiments.

Results

Based on the study, it is found that the expression of miR-205–3p is down-regulated, while that of CXCL11 is up-regulated in GC cell lines. By regulating CXCL11, miR-205–3p inhibits Akt activation, reduces the proliferation and invasion of GC cells, promotes cell apoptosis, induces senescence of GC cells, and secretes immunostimulatory SASP factor. The animal experiments confirm that miR-205–3p promotes cell senescence, down-regulates the immunosuppressive signal induced by PD-L1, and promotes secretion of immunostimulatory SASP factor, so that more T cells are recruited in blood and tumors.

Conclusions

This study revealed the molecular mechanism of miR-205–3p in inhibiting proliferation and invasion and inducing senescence of GC cells by regulating CXCL11 and Akt pathways in animal and cell experiments.

中文翻译：

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MicroRNA-205-3p 通过抑制增殖和诱导衰老在胃癌中的肿瘤抑制作用

背景

我们之前的研究表明 CXCL11 可以发挥免疫调节作用。在本研究中，我们研究了 CXCL11 的调节因子（miR-205-3p）和 miR-205-3p 作为胃癌（GC）抑癌基因的机制。

材料和方法

使用生物信息学方法揭示了 miR-205-3p 和 CXCL11 之间的靶标关系。本研究通过qRT-PCR和Western blotting检测miR-205-3p和CXCL11的表达。此外，还测定了 Akt、PD-L1、p16、p21 和衰老相关分泌表型 (SASP) 因子的表达。通过转染、Transwell 测定、片剂克隆、流式细胞术和衰老相关β-半乳糖苷酶（SA-β-gal）染色等方法评估miR-205对GC细胞增殖、侵袭和衰老的影响. 此外，使用免疫组织化学、流式细胞术和 SA-β-gal 等方法在动物实验中验证了效果。

结果

根据研究发现，在GC细胞系中miR-205-3p的表达下调，而CXCL11的表达上调。miR-205-3p通过调节CXCL11，抑制Akt活化，减少GC细胞的增殖和侵袭，促进细胞凋亡，诱导GC细胞衰老，分泌免疫刺激SASP因子。动物实验证实，miR-205-3p促进细胞衰老，下调PD-L1诱导的免疫抑制信号，促进免疫刺激性SASP因子的分泌，从而使更多的T细胞募集到血液和肿瘤中。

结论

本研究揭示了miR-205-3p在动物和细胞实验中通过调节CXCL11和Akt通路抑制GC细胞增殖和侵袭以及诱导GC细胞衰老的分子机制。