SNORA38B promotes proliferation, migration, invasion and epithelial-mesenchymal transition of gallbladder cancer cells via activating TGF-β/Smad2/3 signaling

Autor: Yiyu Qin, Jian Li, Hongchao Han, Yongliang Zheng, Haiming Lei, Yang Zhou, Hongyan Wu, Guozhe Zhang, Xiang Chen, Zhengping Chen
Jazyk: angličtina
Rok vydání: 2023
Předmět:
Zdroj: European Journal of Histochemistry, Vol 67, Iss 4 (2023)
Druh dokumentu: article
ISSN: 1121-760X
2038-8306
DOI: 10.4081/ejh.2023.3899
Popis: Evidence has shown that small nucleolar RNAs (snoRNAs) participate in the tumorigenesis in multiple cancers, including gallbladder cancer (GBC). Our results showed that SNORA38B level was increased in GBC tissues compared to adjacent normal tissues. Thus, this research aimed to explore the role and molecular mechanisms of SNORA38B in GBC. SNORA38B level between normal and GBC tissues was evaluated by RT-qPCR. Cell proliferation, apoptosis, migration, and invasion were tested by EdU assay, TUNEL staining and transwell assay, respectively on human intrahepatic biliary epithelial cells (HIBEpiCs) and the GBC cell lines, NOZ and GBC-SD. Expression of proteins in GBC cells was evaluated by immunofluorescence and Western blot assays. We found that, relative to normal tissues, SNORA38B level was notably elevated in GBC tissues. SNORA38B overexpression obviously enhanced GBC cell proliferation, migration, invasion and epithelial-mesenchymal transition (EMT), but weakened cell apoptosis. Conversely, SNORA38B downregulation strongly suppressed the proliferation and EMT of GBC cells and induced cell apoptosis and ferroptosis, whereas these phenomena were obviously reversed by TGF-β. Meanwhile, SNORA38B downregulation notably reduced the levels of phosphorylated-Smad2 and phosphorylated-Smad3 in GBC cells, whereas these levels were elevated by TGF-β. Collectively, downregulation of SNORA38B could inhibit GBC cell proliferation and EMT and induce ferroptosis via inactivating TGF-β1/Smad2/3 signaling. These findings showed that SNORA38B may be potential target for GBC treatment.
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