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Hsa_circ_0001859 promotes NSCLC progression through the miRNA-101-3p/MMP1 axis
Jianxin Tan1, Zhenyu Fan2, Rongguo Lu1
1Lung Transplant Center, Department of Thoracic Surgery, The Affiliated Wuxi People's Hospital of Nanjing Medical University, Wuxi People's Hospital, Wuxi Medical Center, Nanjing Medical University, Wuxi, Jiangsu, China.
Background:
Non-small cell lung cancer (NSCLC) is a prevalent form of lung cancer characterized by a significant incidence and mortality rate in China. Most patients are diagnosed at an advanced stage. Circ_0001859 served as an exon circular RNA, but its specific role in NSCLC remained extensively unexplored.
Methods:
Quantitative Real-Time-Polymerase Chain Reaction (qRT-PCR) and western blotting were utilized to detect messenger RNA (mRNA) and protein expression levels in NSCLC tissues and cells. Cell proliferation was assessed by Cell Counting Kit-8 (CCK-8) and colony formation assays. Cell migration and invasion were evaluated by transwell assay. Mechanistically, the mechanisms and target binding relationship between circ_0001859, miR-101-3p and MMP1 were assessed through the luciferase reporter and RNA immunoprecipitation (RIP) assays. In vivo xenograft model was established to examine the impact of circ_0001859.
Results:
Circ_0001859 was significantly overexpressed in NSCLC tissues and cells. Functional studies demonstrated that silencing circ_0001859 significantly impeded the malignant phenotype of NSCLC cells. Bioinformatics analysis and rescue experiments disclosed that circ_0001859 functioned as a sponge for miR-101-3p, modulating MMP1 expression and thereby controlling NSCLC development and metastasis. The role of circ_0001859/miR-101-3p/MMP1 axis was validated in xenograft tumor models in vivo.
Conclusions:
Our research findings demonstrated that circ_0001859 engaged in regulating NSCLC growth and metastasis via the miR-101-3p/MMP1 pathway. These studies presented the first investigation into the precise function and putative regulatory mechanism of circ_0001859 in NSCLC, providing valuable insights towards prognostic indicators and therapeutic targets for malignant tumors.
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