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

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. Graphical Abstract

Automated summary

This study found that KLK11 is downregulated in gastric cancer and reduces the proliferative capacity of gastric cancer cells by inhibiting the phosphorylation of mTOR/4E-BP1. On the other hand, miR-1304 promotes gastric cancer cell proliferation by inhibiting KLK11. KLK11 can also limit the proliferation of gastric cancer cells in vivo.