MiR-144-3p inhibits gastric cancer progression and stemness via directly targeting GLI2 involved in hedgehog pathway.
MiR-144-3p inhibits gastric cancer progression and stemness via directly targeting GLI2 involved in hedgehog pathway.
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DOI：
10.1186/s12967-021-03093-w
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发表时间：
2021-10-17
影响因子：
7.4
通讯作者：
Chen L
中科院分区：
文献类型：
--
作者：
Lu Y;Zhang B;Wang B;Wu D;Wang C;Gao Y;Liang W;Xi H;Wang X;Chen L
胃癌（GC）是全球第五大最常见的癌症。由于预后不佳，迫切需要在GC中找到新的治疗靶标。已有证据表明，miRNAs在肿瘤的发生和发展中起着重要的调控作用。GLI家族锌指2（GLI 2）已被报道在多种恶性肿瘤中上调并促进癌症进展。在这项研究中，我们专注于识别GLI 2靶向的miRNAs，并阐明GC的潜在机制。从胃切除术患者中收集成对的新鲜胃癌组织。GLI 2和miRNAs在胃癌组织和细胞系中均有表达。生物信息学分析用于预测GLI 2靶向miRNA，双荧光素酶报告基因分析用于靶点验证。CCK-8法、克隆形成法、transwell法和流式细胞术检测胃癌细胞的增殖、迁移、侵袭和细胞周期。采用肿瘤球形成实验和流式细胞术检测胃癌干细胞的干细胞特性。建立裸鼠异种移植模型以研究miR-144- 3 p在体内的作用。GLI 2在GC中经常上调，表明生存率低。胃癌组织中miR-144- 3 p表达下调，与GLI 2表达呈负相关。GLI 2是miR-144- 3 p的直接靶基因。miR-144- 3 p过表达可抑制胃癌细胞的增殖、迁移和侵袭。增强的miR-144- 3 p表达抑制GCSC的肿瘤球形成和CD 44表达。GLI 2表达的恢复部分逆转了miR-144- 3 p的抑制作用。异种移植实验表明，miR-144- 3 p对胃癌的体内成瘤有抑制作用。miR-144- 3 p在胃癌中表达下调，是一种重要的肿瘤抑制因子。从机制上讲，miR-144- 3 p至少部分通过调节GLI 2表达来抑制胃癌进展和干性。在线版本包含补充材料，可通过10.1186/s12967-021-03093-w获得。
Gastric cancer (GC) is the fifth most commonly diagnosed cancer worldwide. Due to the dismal prognosis, identifying novel therapeutic targets in GC is urgently needed. Evidences have shown that miRNAs played critical roles in the regulation of tumor initiation and progression. GLI family zinc finger 2 (GLI2) has been reported to be up-regulated and facilitate cancer progression in multiple malignancies. In this study, we focused on identifying GLI2-targeted miRNAs and clarifying the underlying mechanism in GC. Paired fresh gastric cancer tissues were collected from gastrectomy patients. GLI2 and miRNAs expression were detected in gastric cancer tissues and cell lines. Bioinformatics analysis was used to predict GLI2-targeted miRNAs and dual-luciferase reporter assay was applied for target verification. CCK-8, clone formation, transwell and flow cytometry were carried out to determine the proliferation, migration, invasion and cell cycle of gastric cancer cells. Tumorsphere formation assay and flow cytometry were performed to detail the stemness of gastric cancer stem cells (GCSCs). Xenograft models in nude mice were established to investigate the role of the miR-144-3p in vivo. GLI2 was frequently upregulated in GC and indicated a poor survival. Meanwhile, miR-144-3p was downregulated and negatively correlated with GLI2 in GC. GLI2 was a direct target gene of miR-144-3p. MiR-144-3p overexpression inhibited proliferation, migration and invasion of gastric cancer cells. Enhanced miR-144-3p expression inhibited tumorsphere formation and CD44 expression of GCSCs. Restoration of GLI2 expression partly reversed the suppressive effect of miR-144-3p. Xenograft assay showed that miR-144-3p could inhibit the tumorigenesis of GC in vivo. MiR-144-3p was downregulated and served as an essential tumor suppressor in GC. Mechanistically, miR-144-3p inhibited gastric cancer progression and stemness by, at least in part, regulating GLI2 expression. The online version contains supplementary material available at 10.1186/s12967-021-03093-w.
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DOI：
10.1073/pnas.1801348115
发表时间：
2018-06-26
影响因子：
11.1
作者：
Tang, Yen-An;Chen, Yu-feng;Yu, Qiang
通讯作者：
Yu, Qiang
影响因子：
2.4
作者：
Bhaskaran M;Mohan M
通讯作者：
Mohan M
DOI：
10.1016/j.omtn.2017.06.005
发表时间：
2017-09-15
期刊：
Molecular therapy. Nucleic acids
影响因子：
--
作者：
Chakraborty C;Sharma AR;Sharma G;Doss CGP;Lee SS
通讯作者：
Lee SS
影响因子：
5.8
作者：
Liu C;Su C;Chen Y;Li G
通讯作者：
Li G
影响因子：
6
作者：
Larsen LJ;Møller LB
通讯作者：
Møller LB