CircSMARCA5 inhibits glycolysis and suppresses proliferation and invasion of gastric cancer cells through miR-4295/PTEN axis

Juan CAI; Zhiqiang CHEN; Xueliang ZUO

doi:10.19401/j.cnki.1007-3639.2022.04.002

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CircSMARCA5 inhibits glycolysis and suppresses proliferation and invasion of gastric cancer cells through miR-4295/PTEN axis

Article | 更新时间：2025-12-31

- CircSMARCA5 inhibits glycolysis and suppresses proliferation and invasion of gastric cancer cells through miR-4295/PTEN axis
- China Oncology Vol. 32, Issue 4, Pages: 298-308(2022)
- 作者机构：
  
  1. 皖南医学院第一附属医院（弋矶山医院）肿瘤内科,重大疾病非编码RNA转化研究安徽普通高校重点实验室,安徽芜湖 241001
  2. 南京医科大学第一附属医院肝胆中心,江苏南京 210029
  3. 皖南医学院第一附属医院（弋矶山医院）胃肠外科,安徽芜湖 241001
- 作者简介：
- 基金信息：
- DOI：10.19401/j.cnki.1007-3639.2022.04.002
  CLC： R735.2
- Received：20 November 2021，
  
  Revised：2022-03-01，
  
  Published：30 April 2022
- 稿件说明：
移动端阅览
Juan CAI, Zhiqiang CHEN, Xueliang ZUO. CircSMARCA5 inhibits glycolysis and suppresses proliferation and invasion of gastric cancer cells through miR-4295/PTEN axis[J]. China Oncology, 2022, 32(4): 298-308.
DOI：

Juan CAI, Zhiqiang CHEN, Xueliang ZUO. CircSMARCA5 inhibits glycolysis and suppresses proliferation and invasion of gastric cancer cells through miR-4295/PTEN axis[J]. China Oncology, 2022, 32(4): 298-308. DOI： 10.19401/j.cnki.1007-3639.2022.04.002.

摘要

背景与目的：

胃癌是常见的消化系统恶性肿瘤。作者既往研究发现circSMARCA5在胃癌中表达降低并能够抑制胃癌进展

但其具体机制目前仍不清楚。本研究探究circSMARCA5抑制胃癌细胞增殖和侵袭的分子机制。

方法：

采用细胞计数试剂盒-8（cell counting kit-8

CCK-8）和transwell实验检测过表达circSMARCA5对胃癌细胞增殖和侵袭能力的影响。通过检测细胞外酸化率、葡萄糖摄取水平和乳酸生成量

分析过表达circSMARCA5对胃癌细胞糖酵解的影响。采用实时荧光定量聚合酶链式反应（real-time fluorescent quantitative polymerase chain reaction

RTFQ-PCR）检测circSMARCA5、miR-4295和

PTEN

的基因表达

采用蛋白质印迹法（Western blot）检测GLUT1和LDHA的蛋白水平。建立BACB/c裸小鼠皮下移植瘤模型

观察过表达circSMARCA5对移植瘤生长的影响

利用免疫组织化学方法检测两组皮下瘤中GLUT1、LDHA的表达水平及Ki-67增殖指数。通过双荧光素酶报告基因实验、Pearson相关性分析和RNA免疫沉淀（RNA immunoprecipitation

RIP）实验检测circSMARCA5与miR-4295、miR-4295及PTEN的靶向调控关系。

结果：

过表达circSMARCA5能够抑制胃癌细胞增殖和侵袭。CircSMARCA5过表达组细胞的糖酵解速率、糖酵解能力值、葡萄糖摄取水平和乳酸生成量均低于对照组。此外

过表达circSMARCA5能够抑制裸小鼠皮下移植瘤的生长。进一步研究发现

circSMARCA5可发挥分子海绵作用下调miR-4295表达

而miR-4295通过与PTEN mRNA的3

#x02032;-UTR结合抑制PTEN表达。在circSMARCA5过表达组细胞中上调miR-4295或下调PTEN表达可部分逆转circSMARCA5对胃癌细胞增殖、侵袭和糖酵解的影响。

结论：

CircSMARCA5通过竞争性结合miR-4295上调PTEN表达

调控细胞糖酵解

从而抑制胃癌细胞的增殖和侵袭。

Abstract

Background and purpose:

Gastric cancer is one of the most common malignant tumors of digestive system. Previous study demonstrated that circSMARCA5 was downregulated and could function as a tumor suppressor in gastric cancer. However

the molecular mechanism has not yet been documented. This study aimed to investigate the effects of circSMARCA5 on the proliferation and invasion of gastric cancer cells and their molecular mechanisms.

Methods:

Cell counting kit-8 (CCK-8) assays and tr

answell assays were performed to examine the cell proliferative and invasive abilities

respectively. The effect of circSMARCA5 on gastric cancer cell glycolysis was assessed by detecting the extracellular acidification rate

glucose uptake level and lactate production. Real-time fluorescent quantitative polymerase chain reaction (RTFQ-PCR) assay was performed to detect the expression levels of circSMARCA5

miR-4295 and PTEN. The levels of GLUT1 and LDHA were measured by Western blot assay. The transplanted xenograft model in nude mice was established

and the effects of circSMARCA5 on the tumor growth were observed. Immunohistochemistry assays were performed to examine the expression levels of GLUT1

LDHA and Ki-67 proliferation index in xenograft tumors. Dual luciferase reporter gene assays

Pearson's correlation analysis and RNA immunoprecipitation (RIP) assays were used to confirm the targeting relationship of circSMARCA5 and miR-4295 as well as miR-4295 and PTEN.

Results:

CircSMARCA5 overexpression inhibited the proliferation and invasion of gastric cancer cells. Compared to the control group

the glycolysis rate

glycolysis capacity

glucose uptake and lactate production in the circSMARCA5-overexpresing group were significantly decreased. In addition

nude mouse transplanted xenograft assays showed that the volume and the weight of the tumors in the circSMARCA5-overexpressing group were lower compared with the control group. Further studies indicated that circSMARCA5 acted as a molecular sponge to inhibit the expression of miR-4295. Besides

miR-4295 could inhibit the expression of PTEN by binding with the 3'-UTR of PTEN mRNA. Rescue experiments by upregulating miR-4295 or downregulating PTEN expression in the circSMARCA5-overexpressing gastric cancer cells were performed

and the results showed that upregulation of miR-4295 or PTEN knockdown could abolish the inhibitory effects of circSMARCA5 overexpression on cell proliferation

invasion and glycolysis.

Conclusion:

CircSMARCA5 su

ppresses the proliferation and invasion of gastric cancer cells by targeting miR-4295

increasing the expression level of PTEN and subsequently regulating glycolysis.

关键词

Keywords

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