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Analysis of Combinatorial miRNA Treatments to Regulate Cell Cycle and Angiogenesis
Published on: March 30, 2019
Circular RNA hsa_Circ_0007552 inhibits lung adenocarcinoma proliferation, migration and invasion via the
Yanping Lin1, Rong Li1, Xin Shen1
1Department of Digestive Oncology, The Third Affiliated Hospital of Kunming Medical University, Yunnan Cancer Hospital, Peking University Cancer Hospital Yunnan, Kunming, Yunnan, China.
Objectives:
Circular RNAs (circRNAs) are a class of non-coding RNAs with diverse pathophysiological functions. However, the functional roles and molecular mechanisms of circRNAs in lung adenocarcinoma (LUAD) remain to be further elucidated.
Methods:
The expression levels of Circ_0007552 (Circ_RILPL1), miR-7974, and BRCA1-associated protein 1 (BAP1) mRNA in LUAD tissues and cells were detected by quantitative real-time PCR (qRT-PCR). Cell viability, migration, and invasion capabilities were evaluated using the Cell Counting Kit-8 (CCK-8), colony formation assay, wound healing assay, and Transwell migration and invasion assays. A xenograft tumor model in nude mice was established to assess the in vivo effects of Circ_0007552 on LUAD by measuring tumor size, weight, and growth rate. Bioinformatics analysis and dual-luciferase reporter gene assays were conducted to validate the interactions among Circ_0007552, miR-7974, and BAP1. Western blot was performed to detect the protein expression of BAP1.
Results:
Circ_0007552 exhibited low expression in LUAD tissues and cells, correlating with clinicopathological features such as tumor size, lymph node metastasis, clinical stage, and poor prognosis. Both in vitro and in vivo experiments demonstrated that Circ_0007552 overexpression suppressed malignant biological behaviors of LUAD cells, whereas its knockdown exerted opposite effects. Mechanistically, Circ_0007552 functioned as a competing endogenous RNA (ceRNA) for miR-7974, negatively regulating its expression. Overexpression of miR-7974 partially reversed the tumor-suppressive effects of Circ_0007552 on LUAD cells. Furthermore, BAP1 was identified as a downstream target of miR-7974, and Circ_0007552 positively modulated BAP1 expression.
Conclusion:
Circ_0007552 inhibits the development, progression, and metastasis of lung cancer by sponging miR-7974 to upregulate BAP1 expression. The present study further elucidates the underlying molecular mechanisms driving lung cancer progression.
Insights
Circular RNA Circ_0007552 inhibits lung adenocarcinoma (LUAD) progression by sponging miR-7974, upregulating BRCA1-associated protein 1 (BAP1). This finding elucidates novel molecular mechanisms in lung cancer development.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Circular RNAs (circRNAs) are non-coding RNAs with significant roles in various diseases.
- The specific functions and mechanisms of circRNAs in lung adenocarcinoma (LUAD) require further investigation.
Purpose of the Study:
- To investigate the role and molecular mechanism of Circ_0007552 in the development and progression of lung adenocarcinoma.
- To explore the regulatory network involving Circ_0007552, miR-7974, and BAP1 in LUAD.
Main Methods:
- Quantitative real-time PCR (qRT-PCR) to measure expression levels of Circ_0007552, miR-7974, and BAP1 mRNA.
- Cellular assays (CCK-8, colony formation, wound healing, Transwell) to assess LUAD cell viability, migration, and invasion.
- In vivo xenograft model in nude mice to evaluate the effect of Circ_0007552 on tumor growth.
- Bioinformatics analysis, dual-luciferase reporter assays, and Western blot to elucidate molecular interactions and protein expression.
Main Results:
- Circ_0007552 was underexpressed in LUAD tissues and correlated with poor prognosis.
- Overexpression of Circ_0007552 suppressed LUAD cell proliferation, migration, and invasion, while knockdown promoted these behaviors.
- Circ_0007552 acts as a competing endogenous RNA (ceRNA) for miR-7974, negatively regulating its expression.
- BAP1 was identified as a downstream target of miR-7974, and Circ_0007552 positively modulated BAP1 expression.
Conclusions:
- Circ_0007552 inhibits LUAD progression and metastasis by sponging miR-7974, thereby upregulating BAP1 expression.
- This study reveals a novel circRNA-mediated regulatory pathway crucial for understanding lung cancer progression.
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