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Analysis of Combinatorial miRNA Treatments to Regulate Cell Cycle and Angiogenesis
Published on: March 30, 2019
CircSFMBT2 Plays an Oncogenic Role in Lung Adenocarcinoma Depending on the miR-1305/SALL4 Axis
Xuan Zhao1, Xiaojing Xing1, Yongkai Wu2
1Department of Hematology and Breast Medicine, Cancer Hospital of China Medical University, No. 44, Xiaoheyan Road, Dadong District, Shenyang, 110801, Liaoning, China.
Abstract:
Circular RNAs (circRNAs) exhibit significant functions in diverse malignant tumors, including lung adenocarcinoma (LUAD). In this study, we aimed to elucidate the role of circRNA scm like with four mbt domains 2 (circSFMBT2) in LUAD. Quantitative real-time polymerase chain reaction (qRT-PCR), western blot assay or immunohistochemistry (IHC) assay was performed for quantification of circSFMBT2, microRNA-1305 (miR-1305), spalt like transcription factor 4 (SALL4), proliferating Cell Nuclear Antigen (PCNA) or Ki-67. 5-ethynyl-2'-deoxyuridine (EdU) assay, transwell assay and flow cytometry analysis were applied to analyze cell proliferation, metastasis and apoptosis, respectively. Mouse xenograft model was established to explore the function of circSFMBT2. Dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay were used to estimate the relationship between miR-1305 and circSFMBT2 or SALL4. CircSFMBT2 was upregulated in LUAD and related to advanced TNM stage and poor prognosis. CircSFMBT2 knockdown suppressed cell proliferation, metastasis, glycolysis and induced apoptosis in LUAD cells in vitro as well as tumor formation in vivo. CircSFMBT2 directly targeted miR-1305, and miR-1305 inhibition reversed circSFMBT2 knockdown-mediated inhibitory effects on LUAD malignant behaviors. SALL4 was the target gene of miR-1305. MiR-1305 overexpression repressed the malignant phenotypes of LUAD cells, while SALL4 enhancement abated the effects. CircSFMBT2 aggravated the progression of LUAD by the miR-1305/SALL4 axis, which might provide a diagnostic and prognostic marker for LUAD.
Insights
Circular RNA SFMBT2 (circSFMBT2) promotes lung adenocarcinoma (LUAD) progression by targeting the miR-1305/SALL4 pathway. This circRNA may serve as a potential diagnostic and prognostic marker for LUAD patients.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Circular RNAs (circRNAs) play critical roles in various cancers, including lung adenocarcinoma (LUAD).
- The specific function of circRNA scm like with four mbt domains 2 (circSFMBT2) in LUAD remains largely unexplored.
Purpose of the Study:
- To investigate the role and mechanism of circSFMBT2 in the progression of lung adenocarcinoma.
- To explore circSFMBT2 as a potential diagnostic and prognostic biomarker for LUAD.
Main Methods:
- Quantitative real-time polymerase chain reaction (qRT-PCR), western blot, and immunohistochemistry (IHC) were used to assess molecule expression.
- Cellular assays (EdU, transwell, flow cytometry) and a mouse xenograft model were employed to evaluate LUAD cell behaviors and tumor growth.
- Dual-luciferase reporter and RNA immunoprecipitation (RIP) assays were conducted to confirm molecular interactions.
Main Results:
- CircSFMBT2 was found to be upregulated in LUAD tissues and correlated with advanced TNM stage and poor prognosis.
- Knockdown of circSFMBT2 inhibited LUAD cell proliferation, metastasis, and glycolysis, while inducing apoptosis in vitro and suppressing tumor formation in vivo.
- CircSFMBT2 directly targeted microRNA-1305 (miR-1305), and miR-1305 targeted spalt like transcription factor 4 (SALL4).
- The circSFMBT2/miR-1305/SALL4 axis was identified as a key pathway driving LUAD progression.
Conclusions:
- CircSFMBT2 promotes LUAD progression by sponging miR-1305 and upregulating SALL4.
- CircSFMBT2 acts as an oncogene in LUAD and represents a potential diagnostic and prognostic biomarker.
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