Gastric cancer (GC) is prevalent worldwide but has a dismal prognosis, and its molecular and pathogenic pathways remain unknown. Kallikrein 11 has a reduced expression in gastric cancer and may be a promising biomarker. Herein, the function of KLK11 in GC and its regulatory mechanism was studied. Gene sequencing and quantitative reverse transcription-polymerase chain reaction (qRT-PCR) 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. 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. These findings reveal a promising strategy to prevent and treat GC by targeting the KLK11-mediated mTOR/4E-BP1 cascade.

中文翻译：

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miR-1304 靶向 KLK11，通过 mTOR 信号通路调节胃癌细胞增殖。

胃癌（GC）在世界范围内普遍存在，但预后不佳，其分子和致病途径仍不清楚。激肽释放酶 11 在胃癌中表达降低，可能是一种有前途的生物标志物。本文研究了KLK11在GC中的功能及其调控机制。采用基因测序和定量逆转录聚合酶链反应（qRT-PCR）测定胃癌和癌前病变中KLK11的表达。细胞功能测试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。使用蛋白质印迹分析 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 磷酸化程度来降低 GC 细胞的增殖能力。相反，miR-1304 通过抑制 KLK11 来增加 GC 细胞增殖。此外，KLK11 能够限制体内 GC 细胞增殖。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 的有前途的策略。