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Analysis of Combinatorial miRNA Treatments to Regulate Cell Cycle and Angiogenesis
Published on: March 30, 2019
Deficiency of circ_0103809 Attenuates Non-small Cell Lung Cancer Malignant Progression by Controlling
Xueliang Yang1, Xinchun Chai1, Yongming Song1
1Department of Thoracic Surgery, Shanxi Hospital Affiliated to Cancer Hospital, Shanxi Province Cancer Hospital, Chinese Academy of Medical Sciences, Cancer Hospital Affiliated to Shanxi Medical University, No. 3, Beihewan East Street, Worker Street, Xinghualing District, Taiyuan, Shanxi, China.
Abstract:
Circular RNAs are vital players in tumorigenesis. We held the purpose to investigate the role and mechanism of circ_0103809 in non-small cell lung cancer (NSCLC). The expressions of circ_0103809, miR-153-3p and HDAC1 mRNA were determined using quantitative real-time PCR assay, and HDAC1 protein was quantified using western blot analysis. MTT, EdU, flow cytometry, tube-formation, wound healing and tube-formation assays were conducted for functional analysis. The predicted relationship among circ_0103809, miR-153-3p and HDAC1 was ascertained using dual-luciferase analysis, RIP assay and pull-down analysis. Animal models were further constructed to realize circ_0103809's role in vivo. Circ_0103809 was upregulated NSCLC specimens, cells and serum-derived exosomes. Serum exosomal circ_0103809 had the potency to be a diagnostic biomarker for NSCLC. Circ_0103809 silencing inhibited NSCLC cell growth, metastasis and angiogenesis and triggered cell cycle arrest and apoptosis. Circ_0103809 deficiency also suppressed the growth of transplanted tumors. Circ_0103809 acted as the miR-153-3p sponge, and the biological effects of circ_0103809 knockdown were relieved by miR-153-3p inhibition. HDAC1 was directly targeted by miR-153-3p, and miR-153-3p enrichment inhibited NSCLC cell malignant phenotypes by sequestering HDAC1. Circ_0103809 knockdown repressed NSCLC malignant progression partly by regulating miR-153-3p/HDAC1 signaling.
Insights
Circular RNA circ_0103809 promotes non-small cell lung cancer (NSCLC) progression by sponging miR-153-3p and upregulating HDAC1. Circ_0103809 may serve as a diagnostic biomarker for NSCLC.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Circular RNAs (circRNAs) are increasingly recognized for their roles in cancer development.
- Non-small cell lung cancer (NSCLC) is a major cause of cancer-related mortality, necessitating novel diagnostic and therapeutic targets.
Purpose of the Study:
- To investigate the role and underlying mechanism of circ_0103809 in the progression of non-small cell lung cancer (NSCLC).
- To evaluate the potential of circ_0103809 as a diagnostic biomarker for NSCLC.
Main Methods:
- Quantitative real-time PCR and western blot to assess expression levels of circ_0103809, miR-153-3p, and HDAC1.
- In vitro assays (MTT, EdU, flow cytometry, wound healing, tube formation) to analyze functional roles.
- Dual-luciferase, RIP, and pull-down assays to confirm molecular interactions.
- In vivo animal models to validate findings.
Main Results:
- Circ_0103809 was significantly upregulated in NSCLC tissues, cells, and serum-derived exosomes, showing potential as a diagnostic biomarker.
- Silencing circ_0103809 inhibited NSCLC cell proliferation, migration, angiogenesis, and induced apoptosis and cell cycle arrest.
- Circ_0103809 functioned as a miR-153-3p sponge, and miR-153-3p targeted HDAC1, thereby inhibiting NSCLC malignancy.
- Knockdown of circ_0103809 suppressed tumor growth in vivo.
Conclusions:
- Circ_0103809 promotes NSCLC progression by modulating the miR-153-3p/HDAC1 axis.
- Circ_0103809 represents a potential diagnostic biomarker and therapeutic target for NSCLC.
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