EIF4A3诱导的圈RNA_ 0001860通过miR-618/HMGA2轴促进胃癌细胞的生长、侵袭和免疫逃避。

IF 2.2 4区 医学 Q3 ONCOLOGY Neoplasma Pub Date : 2024-10-01 DOI:10.4149/neo_2024_240502N196
Xiaoyi Zhang, Jiaqi Li, Qian Zhang
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引用次数: 0

摘要

胃癌是一种全球常见的癌症,预后很差。Circle RNA_ 0001860(circ_0001860)在多种癌症中调控失调,并参与癌症的发展。然而,它在胃癌中的参与情况仍不清楚。用针对 circ_0001860 的 shRNA 转染 AGS 和 HGC-27 细胞,以降低 circ_0001860 的水平。通过细胞计数试剂盒-8、5-乙炔基-2'-脱氧尿苷(EdU)掺入、Transwell、ELISA、双荧光素酶报告、RIP、RNA pull-down和Western印迹等方法分析了circ_0001860在胃癌中的功能。裸鼠皮下接种带有慢病毒包装的 sh-circ_0001860 的 AGS 细胞,通过免疫组化检测确定 sh-circ_0001860 在胃癌中的作用。敲除 circ_0001860 能降低胃癌细胞的活力、EdU 阳性细胞的百分比、侵袭细胞的数量、IL-10 和 TGF-β 的浓度,同时提高 IFN-γ 和 IL-2 的浓度。sh-circ_0001860 对胃癌细胞生长、侵袭和免疫逃避的抑制作用在 miR-618 敲除或 HMGA2 过表达后被取消。此外,EIF4A3 能正向调节胃癌细胞中 circ_0001860 的水平。在体内,沉默circ_0001860可减少肿瘤的大小和重量以及HMGA2和IL-10的表达,但可提高miR-618和IFN-γ的水平。总之,circle RNA_ 0001860由EIF4A3诱导,通过miR-618/HMGA2轴增强胃癌的增殖、侵袭和免疫逃避。
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EIF4A3-induced circle RNA_ 0001860 promotes growth, invasion, and immune evasion of gastric cancer cells through the miR-618/HMGA2 axis.

Gastric cancer is a globally common type of cancer with a dismal prognosis. Circle RNA_ 0001860 (circ_0001860) is dysregulated in several cancers and involved in cancer development. Its involvement in stomach cancer, however, remains unclear. AGS and HGC-27 cells were transfected with shRNA against circ_0001860 to knock down the circ_0001860 level. The function of circ_0001860 in gastric cancer was analyzed by cell counting kit-8, 5-ethynyl-2'-deoxyuridine (EdU) incorporation, Transwell, ELISA, dual-luciferase reporter, RIP, RNA pull-down, and western blotting. Nude mice were subcutaneously inoculated with AGS cells with lentivirus-packaged sh-circ_0001860 to determine the role of sh-circ_0001860 in gastric cancer by immunohistochemistry assays. circ_0001860 was upregulated in gastric cancer, indicating a poor prognosis for gastric cancer patients. Knockdown of circ_0001860 reduced gastric cancer cells' viability, the percentage of EdU-positive cells, the numbers of invaded cells, and concentrations of IL-10 and TGF-β while fostering the concentrations of IFN-γ and IL-2. circ_0001860 sponged miR-618 to positively modulate the HMGA2 level in gastric cancer cells. The inhibitory role of sh-circ_0001860 on cell growth, invasion, and immune evasion of gastric cancer was abolished with the miR-618 knockdown or the HMGA2 overexpression. Besides, EIF4A3 positively modulated the circ_0001860 level in gastric cancer cells. In vivo, silencing of circ_0001860 reduced tumor size and weight and the expression of HMGA2 and IL-10 but enhanced the level of miR-618 and IFN-γ. Collectively, circle RNA_ 0001860 was induced by EIF4A3 to enhance proliferation, invasion, and immune evasion of gastric cancer through the miR-618/HMGA2 axis.

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来源期刊
Neoplasma
Neoplasma 医学-肿瘤学
CiteScore
5.40
自引率
0.00%
发文量
238
审稿时长
3 months
期刊介绍: The journal Neoplasma publishes articles on experimental and clinical oncology and cancer epidemiology.
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