Zhang Li-Xiang, Luo Pan-Quan, Wei Zhi-Jian, Xu A-Man, Guo Tao
Department of Gastroenterology, The First Affiliated Hospital of Anhui Medical University, Hefei 230031, Anhui Province, China.
Anhui Provincial Key Laboratory of Digestive Disease, Hefei 230031, Anhui Province, China.
World J Gastrointest Oncol. 2024 Aug 15;16(8):3559-3584. doi: 10.4251/wjgo.v16.i8.3559.
Gastric cancer (GC) is a common malignant tumor, long non-coding RNA and microRNA (miRNA) are important regulators that affect tumor proliferation, metastasis and chemotherapy resistance, and thus participate in tumor progression. CASC19 is a new bio-marker which can promote tumor invasion and metastasis. However, the mechanism by which CASC19 affects the progression of GC through miRNA is not clear.
To explore the role of the CASC19/miR-491-5p/HMGA2 regulatory axis in GC.
To explore the expression and prognosis of CASC19 in GC through clinical samples, and investigate the effects of inhibiting CASC19 on the proliferation, migration, invasion and other functions of GC cells through cell counting Kit-8 (CCK-8), ethynyldeoxyuridine, Wound healing assay, Transwell, Western blot and flow cytometry experiments. The effect of miR-491-5p and HMGA2 in GC were also proved. The regulatory relationship between CASC19 and miR-491-5p, miR-491-5p and HMGA2 were validated through Dual-luciferase reporter gene assay and reverse transcription PCR. Then CCK-8, Transwell, Wound healing assay, flow cytometry and animal experiments verify the role of CASC19/miR-491-5p/HMGA2 regulatory axis.
The expression level of CASC19 is related to the T stage, N stage, and tumor size of patients. Knockdown of the expression of CASC19 can inhibit the ability of proliferation, migration, invasion and EMT conversion of GC cells, and knocking down the expression of CASC19 can promote the apoptosis of GC cells. Increasing the expression of miR-491-5p can inhibit the proliferation of GC cells, miR-491-5p mimics can inhibit EMT conversion, and promote the apoptosis of GC cells, while decreasing the expression of miR-491-5p can promote the proliferation and EMT conversion and inhibit the apoptosis of GC cells. The expression of HMGA2 in GC tissues is higher than that in adjacent tissues. At the same time, the expression level of HMGA2 is related to the N and T stages of the patients. Reducing the level of HMGA2 can promote cell apoptosis and inhibit the proliferation of GC cells. Cell experiments and animal experiments have proved that CASC19 can regulates the expression of HMGA2 through miR-491-5p, thereby affecting the biological functions of GC.
CASC19 regulates the expression of HMGA2 through miR-491-5p to affect the development of GC. This axis may serve as a potential biomarker and therapeutic target of GC.
胃癌（GC）是一种常见的恶性肿瘤，长链非编码RNA和微小RNA（miRNA）是影响肿瘤增殖、转移和化疗耐药性的重要调节因子，从而参与肿瘤进展。CASC19是一种新的生物标志物，可促进肿瘤侵袭和转移。然而，CASC19通过miRNA影响GC进展的机制尚不清楚。
探讨CASC19/miR-491-5p/HMGA2调控轴在GC中的作用。
通过临床样本探讨CASC19在GC中的表达及预后，并通过细胞计数试剂盒-8（CCK-8）、乙炔基脱氧尿苷、伤口愈合试验、Transwell、蛋白质印迹法和流式细胞术实验研究抑制CASC19对GC细胞增殖、迁移、侵袭等功能的影响。还证实了miR-491-5p和HMGA2在GC中的作用。通过双荧光素酶报告基因试验和逆转录PCR验证CASC19与miR-491-5p、miR-491-5p与HMGA2之间的调控关系。然后通过CCK-8、Transwell、伤口愈合试验、流式细胞术和动物实验验证CASC19/miR-491-5p/HMGA2调控轴的作用。
CASC19的表达水平与患者的T分期、N分期和肿瘤大小有关。敲低CASC19的表达可抑制GC细胞的增殖、迁移、侵袭和上皮-间质转化（EMT）能力，敲低CASC19的表达可促进GC细胞凋亡。增加miR-491-5p的表达可抑制GC细胞增殖，miR-491-5p模拟物可抑制EMT转化，并促进GC细胞凋亡，而降低miR-491-5p的表达可促进增殖和EMT转化并抑制GC细胞凋亡。GC组织中HMGA2的表达高于相邻组织。同时，HMGA2的表达水平与患者的N和T分期有关。降低HMGA2水平可促进细胞凋亡并抑制GC细胞增殖。细胞实验和动物实验证明，CASC19可通过miR-491-5p调节HMGA2的表达，从而影响GC的生物学功能。
CASC19通过miR-491-5p调节HMGA2的表达以影响GC的发展。该轴可能作为GC的潜在生物标志物和治疗靶点。
