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Tytuł pozycji:

MiR-144-3p inhibits gastric cancer progression and stemness via directly targeting GLI2 involved in hedgehog pathway

Tytuł:
MiR-144-3p inhibits gastric cancer progression and stemness via directly targeting GLI2 involved in hedgehog pathway
Autorzy:
Yixun Lu
Benlong Zhang
Baohua Wang
Di Wu
Chuang Wang
Yunhe Gao
Wenquan Liang
Hongqing Xi
Xinxin Wang
Lin Chen
Temat:
Gastric cancer
GLI2
MiR-144-3p
Cancer stem cells
Medicine
Źródło:
Journal of Translational Medicine, Vol 19, Iss 1, Pp 1-15 (2021)
Wydawca:
BMC, 2021.
Rok publikacji:
2021
Kolekcja:
LCC:Medicine
Typ dokumentu:
article
Opis pliku:
electronic resource
Język:
English
ISSN:
1479-5876
Relacje:
https://doaj.org/toc/1479-5876
DOI:
10.1186/s12967-021-03093-w
Dostęp URL:
https://doaj.org/article/a1bcbab6eae8419fa3df02e6a5e28a3f  Link otwiera się w nowym oknie
Numer akcesji:
edsdoj.1bcbab6eae8419fa3df02e6a5e28a3f
Czasopismo naukowe
Abstract Background 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. Methods 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. Results 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. Conclusions 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.
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