期刊
ANNALS OF TRANSLATIONAL MEDICINE
卷 9, 期 17, 页码 -出版社
AME PUBLISHING COMPANY
DOI: 10.21037/atm-21-2013
关键词
Gallbladder carcinoma (GBC); stemness; miR-552-3p; repulsive guidance molecule BMP co-receptor a (RGMA); epithelial-mesenchymal transformation (EMT)
资金
- State Key Project on Infectious Diseases of China [2018ZX10723204-002-002]
- National Natural Science Foundation of China [91859205, 81988101, 81830054, 81672777, 81902940, 81902942]
- Natural Science Foundation of Shanghai [19ZR1400300]
- Shanghai Rising-Star Program [17QA1405700]
- Shanghai Top Young Talents Program
- Foundation of Shanghai Shenkang Hospital Development Center [SHDC2020CR2011A, SHDC12016127]
MiR-552-3p promotes the malignant progression of GBC by inhibiting the mRNA of the tumor suppressor gene RGMA, resulting in reactivation of the Akt/beta-catenin signaling pathway.
Background: Gallbladder carcinoma (GBC) remains a highly lethal disease worldwide. MiR-552 family members promote the malignant progression of a variety of digestive system tumors, but the role of miR-552-3p in GBC has not been elucidated. miR-552-3p was predicted to target the 3'-untranslated region (3'UTR) of the mRNA for the tumor suppressor gene repulsive guidance molecule BMP co-receptor a (RGMA). The aim of the present study was to clarify the roles and mechanisms of miR-552-3p targeting RGMA in the malignant progression of GBC. Methods: In vitro: expression of miR-552-3p was detected by real-time quantitative PCR (qRT-PCR) in tumor and non-tumor adjacent tissues (NATs). Lentivirus-miR-552-3p was employed to knockdown this miRNA in GBC cell lines. Stem cell-related transcription factors and markers were assessed by qRT-PCR. Cell Counting Kit-8 (CCK-8), sphere formation and transwell assays were used to determine the malignant phenotypes of GBC cells. Targeting the 3'UTR of RGMA by miR-552-3p was verified by integrated analysis including bioinformatics prediction, luciferase assays, measures of changes of gene expression and rescue experiments. In vivo: mouse models of subcutaneous tumors and lung metastases were established to observe the effect of miR-552-3p on tumorigenesis and organ metastasis, respectively. Results: MiR-552-3p was abnormally highly expressed in GBC tissues and cancer stem cells. Interference with miR-552-3p in SGC-996 and GBC-SD cells significantly inhibited GBC stem cell expansion. Reciprocally, miR-552-3p promoted GBC cell proliferation, migration and invasion both in vitro and in vivo; hence, interference with this miRNA impeded the malignant progression of GBC. Furthermore, the important tumor suppressor gene RGMA was identified as a target of miR-552-3p. The effects of miR-552-3p on cell proliferation and metastasis were abrogated or enhanced by gain or loss of RGMA function, respectively. Mechanistically, miR-552-3p promoted GBC progression by reactivating the Akt/beta-catenin pathway and epithelial-mesenchymal transformation (EMT). Clinically, miR-552-3p correlated with multi-malignant characteristics of GBC and acted as a prognostic marker for GBC outcome. Conclusions: MiR-552-3p promotes the malignant progression of GBC by inhibiting the mRNA of the tumor suppressor gene RGMA, resulting in reactivation of the Akt/beta-catenin signaling pathway.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据