Effects of RP11-757G1.5 on the biological behaviors and cisplatin sensitivity in gastric cancer cells

SHANG Ying; ZHAO Rongkun; YIN Le; SUN Jiaxing; XU Fei; MIAO Lili

doi:10.3969/j.issn.1009-0460.2025.10.003

Abstract：Objective To explore the roles of long non-coding RNA RP11-757G1.5 in regulating biological behaviors and cisplatin sensitivity of gastric cancer cells.Methods The expression levels of RP11-757G1.5 in gastric epithelial cells(GES-1)and human gastric cancer cells(MKN-45,NCI-N87,AGS,and HGC-27)were detected by real-time quantitative PCR(RT-qPCR).Two small interfering RNA(siRNA)sequences targeting RP11-757G1.5(si-757G1.5#1 and si-757G1.5#2)and a negative control sequence(si-NC)were designed and synthesized,and then transfected into MKN-45 and HGC-27 cells.The cells were divided into Control,si-NC,and two interference groups(si-757G1.5#1 and si-757G1.5#2).To investigate the effects of RP11-757G1.5 on malignant behavior and drug sensitivity,the following experiments were performed:cell viability and the half-maximal inhibitory concentration(IC50)of cisplatin were assessed using the Cell Counting Kit-8(CCK-8)assay;cell migration ability was evaluated by wound healing assay;cell invasion ability was analyzed by Transwell assay;and the protein expression levels of matrix metalloproteinase(MMP)-2/9 were detected by Western blot.Results RT-qPCR results showed that the expression of RP11-757G1.5 was significantly upregulated in various gastric cancer cell lines compared with the normal gastric epithelial cell line GES-1(P<0.05).The MKN-45 and HGC-27 cell lines,which exhibited the highest expression levels,were selected for subsequent functional studies.After successful establishment of RP11-757G1.5 knockdown models,a series of functional experiments were performed.The CCK-8 assay revealed that cell proliferation viability was significantly decreased in the two interference groups(si-757G1.5#1 and si-757G1.5#2)compared with the Control and si-NC groups(P<0.05).Meanwhile,drug sensitivity tests based on the CCK-8 method indicated that the interference groups exhibited significantly enhanced chemosensitivity to cisplatin,with IC50 values decreased by approximately 2.3-2.7-fold(P<0.05).In addition,wound healing and Transwell assays demonstrated that the migration and invasion abilities of the cells were also significantly inhibited in the interference groups,as evidenced by markedly reduced wound closure rates and number of invading cells(P<0.05).At the mechanistic level,Western blot analysis showed that the protein expression levels of MMP-2 and MMP-9 were significantly downregulated in the interference groups(P<0.05).Conclusion RP11-757G1.5 is highly expressed in gastric cancer and promotes malignant phenotypes of tumor cells by regulating MMP-2 and MMP-9 expression,while also affecting chemotherapy sensitivity.These findings suggest its potential as a novel therapeutic target for gastric cancer.