CircRNA hsa_circ_0075048 promotes the malignant progression of non-small cell lung cancer by up-regulating HMGB2 expression via targeting miR-1225-5p
Jijiong Zhang and Jinjuan Mao
Department of Respiratory Medicine, Huangshi Central Hospital, Affiliated Hospital of Hubei Polytechnic University, Edong Healthcare Group, Huangshi and Hubei Key Laboratory of Kidney Disease Pathogenesis and Intervention, Hubei, PR China
Corresponding Author: Jinjuan Mao, Department of Respiratory Medicine, Huangshi Central Hospital, Affiliated Hospital of Hubei Polytechnic University, Hubei Key Laboratory of Kidney Disease Pathogenesis and Intervention, No.141 Tianjin Road, Huangshi 435000, China. e-mail: mjj20210312@163.com
Summary. Background. Non-small cell lung cancer (NSCLC) is one of the most common forms of lung cancer. Circular RNAs (circRNAs) have been recognized that can be used as novel molecular markers for cancer therapy. Here, we attempted to identify the role of hsa_circRNA_0075048 (circ_0075048) in NSCLC.
Methods. Quantitative real-time polymerase chain reaction (qRT-PCR) was performed to analyze the levels of hsa_circ_0075048, miR-1225-5p and high mobility group box-2 (HMGB2). Cell proliferation was detected by Cell Counting Kit 8 (CCK8) and 5-Ethynyl-2’-deoxyuridine (EdU) assays. Flow cytometry was used to detect apoptosis. Transwell assay was used to assess cell migration and invasion. Sphere formation ability was tested by cell pellet test. The protein expression levels were detected by western blot and immunohisto-chemistry. Dual-luciferase reporter assay, RNA-pull down and RNA immunoprecipitation (RIP) assays were used to verify the targeting relationships between miR-1225-5p and circ_0075048 or HMGB2. Mice tumor models were constructed to ascertain the effects of circ_0075048 on tumor growth in vivo.
Results. Circ_0075048 was increased in NSCLC tissues and cells. NSCLC cell proliferation, migration, invasion and sphere formation ability were decreased by circ_0075048 knockdown, and cell apoptosis was induced. Downregulation of miR-1225-5p recuperated the effects of circ_0075048 knockdown on NSCLC progression. The effects of miR-1225-5p on cell proliferation, apoptosis, migration, invasion and sphere formation were attenuated by HMGB2 overexpression.
Conclusion. This study indicated that circ_0075048 played an oncogenic role in the development of NSCLC by regulating miR-1225-5p and HMGB2. The data provide more possibilities for the treatment of NSCLC. Histol Histopathol 38, 709-724 (2023)
Key words: circ_0075048, miR-1225-5p, HMGB2, Non-small cell lung cancer
DOI: 10.14670/HH-18-551
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©The Author(s) 2023. Open Access. This article is licensed under a Creative Commons CC-BY International License. |
