miR-1304 targets KLK11 to regulate gastric cancer cell proliferation through the mTOR signaling pathway.

IF 3.3 3区医学 Q2 ONCOLOGY

Carcinogenesis Pub Date : 2024-02-12 DOI:10.1093/carcin/bgad077

Yi Ding, Zehua Wang, Chen Chen, Dongyu Li, Wenjia Wang, Yongxu Jia, Yanru Qin

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引用次数: 0

Abstract

Objective: Gastric cancer (GC) is prevalent worldwide but has a dismal prognosis, and its molecular and pathogenic pathways remain unknown. Kallikrein 11 (KLK11) has a reduced expression in GC and may be a promising biomarker.

Method: Herein, the function of KLK11 in GC and its regulatory mechanism was studied. Gene sequencing and quantitative reverse transcription-polymerase chain reaction were used to determine the expression of KLK11 in GC and precancerous lesions. Cell function tests and flow cytometry were conducted to determine the proliferative capacity and cell cycle of GC cells, respectively. A luciferase reporter test confirmed the interaction between RNA molecules. The mTOR/4E-BP1 signaling pathway was analyzed using western blotting.

Result: KLK11 has a suppressed expression in GC samples. KLK11 decreased the proliferative capacity of GC cells, by inhibiting the degree of mTOR/4E-BP1 phosphorylation. In contrast, miR-1304 increased GC cell proliferation by inhibiting KLK11. Moreover, KLK11 was able to limit in vivo GC cell proliferation.

Conclusion: These findings reveal a promising strategy to prevent and treat GC by targeting the KLK11-mediated mTOR/4E-BP1 cascade.

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miR-1304通过mTOR信号通路靶向KLK11调控胃癌细胞增殖。

胃癌(GC)在世界范围内普遍存在，但预后不佳，其分子和致病途径尚不清楚。Kallikrein 11在胃癌中表达减少，可能是一种有前景的生物标志物。本文研究了KLK11在GC中的作用及其调控机制。采用基因测序和定量逆转录聚合酶链反应(qRT-PCR)检测KLK11在胃癌和癌前病变中的表达。通过细胞功能试验和流式细胞术分别测定GC细胞的增殖能力和细胞周期。荧光素酶报告基因测试证实了RNA分子之间的相互作用。Western blotting分析mTOR/4E-BP1信号通路。KLK11在GC样品中的表达受到抑制。KLK11通过抑制mTOR/4E-BP1磷酸化程度，降低GC细胞的增殖能力。相反，miR-1304通过抑制KLK11增加GC细胞的增殖。此外，KLK11能够限制体内GC细胞的增殖。这些发现揭示了一种通过靶向klk11介导的mTOR/4E-BP1级联来预防和治疗GC的有希望的策略。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Carcinogenesis 医学-肿瘤学

CiteScore

9.20

自引率

2.10%

发文量

审稿时长

1 months

期刊介绍： Carcinogenesis: Integrative Cancer Research is a multi-disciplinary journal that brings together all the varied aspects of research that will ultimately lead to the prevention of cancer in man. The journal publishes papers that warrant prompt publication in the areas of Biology, Genetics and Epigenetics (including the processes of promotion, progression, signal transduction, apoptosis, genomic instability, growth factors, cell and molecular biology, mutation, DNA repair, genetics, etc.), Cancer Biomarkers and Molecular Epidemiology (including genetic predisposition to cancer, and epidemiology), Inflammation, Microenvironment and Prevention (including molecular dosimetry, chemoprevention, nutrition and cancer, etc.), and Carcinogenesis (including oncogenes and tumor suppressor genes in carcinogenesis, therapy resistance of solid tumors, cancer mouse models, apoptosis and senescence, novel therapeutic targets and cancer drugs).