CircRNA hsa_circ_0075048 promotes the malignant progression of non-small cell lung cancer by upregulating HMGB2 expression via targeting miR-1225-5p

Abstract

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 immunohistochemistry. Dual-luciferase reporter assay, RNA-pull down and RNA immunoprecipitation (RIP) assays were used to verify the targeting relationships between miR1225-5p 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.