Clinical Medical College, Jiangsu Vocational College of Medicine, Yancheng, Jiangsu, 224005, PR China.
Department of Science and Technology, Jiangsu Vocational College of Medicine, Yancheng, Jiangsu, 224005, PR China.
Biomed Pharmacother. 2019 Oct;118:109266. doi: 10.1016/j.biopha.2019.109266. Epub 2019 Aug 8.
Gallbladder cancer (GBC) ranks fifth in the most common malignancy of the gastrointestinal tract worldwide. It is reported many small nucleolar RNAs (SNORNs) could regulate the progression of GBC. To identify potential therapeutic targets for GBC, we conducted microarray analysis in GBC tissues and adjacent normal tissues. We found that SNORA21 was downregulated most in gallbladder tumor samples. Therefore, this research aimed to investigate the role of SNORA21 during the tumorigenesis of GBC.
The differential expression of SNORNs between GBC tissues and para-carcinoma tissues were examined by microarray analysis and that were confirmed by qRT-PCR. Cell proliferation was tested by CCK-8 and immunofluorescence. Cell apoptosis and cell cycle in GBC were detected by flow cytometry. Expression of proteins in GBC cells was measured by Western-blot. Transwell assay was used for testing the cell migration and invasion. Xenograft tumor model was established to verify the effect of SNORA21 overexpression on GBC in vivo.
The results revealed that SNORA21 overexpression inhibited the proliferation, migration and invasion of GBC cells. Moreover, overexpression of SNORA21 significantly increased the expression of E-cadherin and decreased the levels of N-cadherin and vimentin. Meanwhile, overexpression of SNORA21 significantly induced apoptosis and G1 arrest of GBC cells. Finally, SNORA21 overexpression significantly suppressed the growth of gallbladder tumors in vivo.
Overexpression of SNORA21 significantly suppressed the tumorigenesis of GBC in vitro and in vivo, which may serve as a potential novel target for the treatment of GBC.
胆囊癌（GBC）在全球范围内是第五种最常见的胃肠道恶性肿瘤。据报道，许多小核仁 RNA（SNORNs）可以调节 GBC 的进展。为了确定 GBC 的潜在治疗靶点，我们对 GBC 组织和相邻正常组织进行了微阵列分析。我们发现 SNORA21 在胆囊肿瘤样本中下调最明显。因此，本研究旨在探讨 SNORA21 在 GBC 发生过程中的作用。
通过微阵列分析和 qRT-PCR 验证了 GBC 组织和癌旁组织中 SNORNs 的差异表达。CCK-8 和免疫荧光法检测细胞增殖。流式细胞术检测 GBC 细胞的凋亡和细胞周期。Western-blot 检测 GBC 细胞中蛋白质的表达。Transwell 检测细胞迁移和侵袭。建立异种移植肿瘤模型以验证 SNORA21 过表达对 GBC 的体内作用。
结果表明，SNORA21 过表达抑制了 GBC 细胞的增殖、迁移和侵袭。此外，SNORA21 的过表达显著增加了 E-钙黏蛋白的表达，降低了 N-钙黏蛋白和波形蛋白的水平。同时，SNORA21 的过表达显著诱导了 GBC 细胞的凋亡和 G1 期阻滞。最后，SNORA21 过表达显著抑制了体内胆囊肿瘤的生长。
SNORA21 的过表达显著抑制了 GBC 的体外和体内肿瘤发生，这可能为 GBC 的治疗提供一个新的潜在靶点。
