Overexpression of SNORA21 suppresses tumorgenesis of gallbladder cancer in vitro and in vivo
Overexpression of SNORA21 suppresses tumorgenesis of gallbladder cancer in vitro and in vivo
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SNORA21 过表达可抑制体外和体内胆囊癌的肿瘤发生
DOI：
10.1016/j.biopha.2019.109266
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发表时间：
2019-10-01
影响因子：
7.5
通讯作者：
Luo, Qiong
中科院分区：
文献类型：
--
作者：
Qin, Yiyu;Zhou, Yang;Luo, Qiong
背景：胆囊癌（GBC）在全球胃肠道最常见的恶性肿瘤中排名第五。研究发现，许多核仁小RNA（SNORNs）参与了GBC的发生、发展过程。为了确定GBC的潜在治疗靶点，我们在GBC组织和邻近正常组织中进行了微阵列分析。我们发现SNORA 21在胆囊肿瘤样品中下调最多。因此，本研究旨在探讨SNORA 21在胆囊癌发生发展中的作用。方法：采用基因芯片技术检测SNORNs在胆囊癌组织和癌旁组织中的差异表达，并通过qRT-PCR技术进行验证。CCK-8法和免疫荧光法检测细胞增殖。流式细胞仪检测GBC细胞凋亡及细胞周期。Western-blot检测GBC细胞蛋白质表达。Transwell法检测细胞的迁移和侵袭能力。结果：SNORA 21过表达可抑制GBC细胞的增殖、迁移和侵袭能力。此外，SNORA 21的过表达显著增加了E-钙粘蛋白的表达，降低了N-钙粘蛋白和波形蛋白的水平。同时，SNORA 21过表达可显著诱导GBC细胞凋亡和G1期阻滞。结论：SNORA 21过表达在体内外均能显著抑制胆囊癌的发生，可能成为治疗胆囊癌的新靶点。
Background: 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.Methods: 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.Results: 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.Conclusion: 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.