Abstract:Objective: To investigate the mechanism of action and clinical relevance of miR-155 and PAD4 in autophagy and proliferation of gastric cancer cells. Methods: Tumor tissue and adjacent non-tumor tissue from 20 gastric cancer patients were collected. The expression differences of miRNA and mRNA between tumor tissue and adjacent tissue were compared using miRNA-seq and RNA-seq technologies, followed by KEGG pathway analysis of differentially expressed mRNA. The expression levels of miR-155, PAD4, and Beclin-1 in tumor tissue and adjacent tissue were detected by quantitative reverse transcription PCR (qRT-PCR). Correlation analysis was conducted on the expression of miR-155, PAD4, and Beclin-1 in tumor tissue. Further analysis was performed on the association between the expression level of miR-155 and patients' gender, age, and tumor malignancy degree. The targeting relationship between miR-155 and PAD4 was determined by luciferase reporter assay. MGC803 cells were transfected with si-NC, si-miR-155, si-miR-155+si-NC, and si-miR-155+si-PAD4, and the expression of miR-155, PAD4, Beclin-1, and p62 was detected by qRT-PCR. Cell proliferation levels were assessed using the CCK-8 method. Results: Compared to adjacent tissues, 295 miRNAs and 348 mRNAs were upregulated, while 195 miRNAs and 174 mRNAs were downregulated in tumor tissues. Upregulated mRNAs were primarily involved in cell proliferation-related signaling pathways such as MAPK and Wnt. In tumor tissues, the expression of miR-155 and Beclin-1 was decreased, whereas PAD4 expression was increased (P<0.05). There was a positive correlation between the expression of miR-155 and Beclin-1, and a negative correlation with PAD4 expression (P<0.05). The expression level of miR-155 was significantly related to the degree of tumor malignancy (P<0.05) but not significantly associated with patients' gender and age (P>0.05). The experimental results indicated that miR-155 could target PAD4. Compared to the si-NC group, the si-miR-155 group showed decreased expression of miR-155 and Beclin-1, and increased expression of PAD4 and p62, resulting in higher cell proliferation levels (P<0.05). Compared to the si-miR-155+si-NC group, the si-miR-155+si-PAD4 group showed reduced expression of PAD4 and p62, increased expression of Beclin-1, and decreased cell proliferation levels (P<0.05). Conclusion: miR-155 promotes autophagy and inhibits proliferation levels in gastric cancer cells by targeting and suppressing the expression of PAD4.
屈振杰, 崔琴. miR-155调控PAD4表达在胃癌细胞自噬和增殖中的作用及其临床相关性研究[J]. 河北医学, 2026, 32(1): 150-156.
QU Zhenjie, CUI Qin. Role of miR-155 in Regulating PAD4 Expression in Autophagy and Proliferation of Gastric Cancer Cells and Its Clinical Relevance. HeBei Med, 2026, 32(1): 150-156.