Wang Xiao-Lei, Zhang Lin, Shang Qing
Department of General Surgery, Xinxiang Central Hospital, Xinxiang 453000, Henan Province, China.
Department of Oncology, The First People's Hospital of Changshu, Suzhou 215501, Jiangsu Province, China.
World J Gastrointest Oncol. 2025 May 15;17(5):105933. doi: 10.4251/wjgo.v17.i5.105933.
Circular RNAs (circRNAs) are critical regulators in tumorigenesis, functioning as microRNA sponges or protein decoys. Although numerous circRNAs have been implicated in gastric cancer progression, the role of hsa_circRNA_101996 remains unclear. This study hypothesizes that hsa_circRNA_101996 promotes gastric cancer cell proliferation and apoptosis the microRNA-577 (miR-577)/high mobility group nucleosome binding domain 5 (HMGN5) axis.
To investigate the role of hsa_circRNA_101996 in gastric cancer proliferation and apoptosis through the miR-577/HMGN5 axis.
Forty-one paired gastric cancer tissues and adjacent non-cancerous tissues were analyzed. Differential circRNA expression was identified using GSE83521 and GSE89143 datasets. miR-577 and HMGN5 were predicted CircInteractome and TargetScan. Functional experiments (MTT, colony formation, Western blot) and dual-luciferase reporter assays were performed in gastric cancer cell lines (OCUM-1, HSC-39). tumorigenesis was validated in nude mice. Statistical analysis included Student's -test and one-way ANOVA ( < 0.05).
Hsa_circRNA_101996 was significantly upregulated in gastric cancer tissues and cell lines compared to adjacent non-cancerous tissues ( < 0.05). Dual-luciferase reporter assays validated the interactions among hsa_circRNA_101996, miR-577, and HMGN5. , gastric cancer cells overexpressing hsa_circRNA_101996 showed significantly increased proliferation and decreased apoptosis compared to controls ( < 0.05). Cells transfected with miR-577 mimics exhibited reduced proliferation and increased apoptosis ( < 0.05). Co-transfection with hsa_circRNA_101996 or HMGN5 reversed the effects of miR-577 mimics. , hsa_circRNA_101996-overexpressing tumors showed increased volume and HMGN5 expression ( < 0.05).
Hsa_circRNA_101996 promotes gastric cancer progression by sponging miR-577 to upregulate HMGN5, suggesting a novel therapeutic target for gastric cancer.
环状RNA(circRNAs)是肿瘤发生过程中的关键调节因子,可作为微小RNA海绵或蛋白质诱饵发挥作用。尽管众多circRNAs已被证明与胃癌进展有关,但hsa_circRNA_101996的作用仍不清楚。本研究假设hsa_circRNA_101996通过微小RNA-577(miR-577)/高迁移率族核小体结合域5(HMGN5)轴促进胃癌细胞增殖并影响其凋亡。
通过miR-577/HMGN5轴研究hsa_circRNA_101996在胃癌增殖和凋亡中的作用。
分析41对胃癌组织及相邻癌旁组织。利用GSE83521和GSE89143数据集鉴定circRNA的差异表达。通过CircInteractome和TargetScan预测miR-577和HMGN5。在胃癌细胞系(OCUM-1、HSC-39)中进行功能实验(MTT、集落形成、蛋白质免疫印迹法)和双荧光素酶报告基因检测。在裸鼠体内验证肿瘤发生情况。统计分析采用Student's t检验和单因素方差分析(P<0.05)。
与相邻癌旁组织相比,hsa_circRNA_101996在胃癌组织和细胞系中显著上调(P<0.05)。双荧光素酶报告基因检测验证了hsa_circRNA_101996、miR-577和HMGN5之间的相互作用。此外,与对照组相比,过表达hsa_circRNA_101996的胃癌细胞增殖显著增加,凋亡减少(P<0.05)。转染miR-577模拟物的细胞增殖减少,凋亡增加(P<0.05)。与hsa_circRNA_101996或HMGN5共转染可逆转miR-577模拟物的作用。此外,过表达hsa_circRNA_101996的肿瘤体积增大,HMGN5表达增加(P<0.05)。
hsa_circRNA_101996通过充当miR-577的海绵来上调HMGN5,从而促进胃癌进展,提示其可作为胃癌的一个新的治疗靶点。