Circ_0067934 promotes non-small cell lung cancer development by regulating miR-1182/KLF8 axis and activating Wnt/β-catenin pathway.

Non-small cell lung cancer (NSCLC) is the primary subtype of lung cancer with high mortality. Circular RNAs (circRNAs) play a crucial role in tumor development and progression. This study aimed to explore the function of circ_0067934 in NSCLC progression and its molecular basis. The levels of circ_0067934, miR-1182 and kruppel like factor 8 (KLF8) were measured by quantitative real-time polymerase chain reaction or western blot assay. Cell viability was detected by Cell Counting Kit-8 (CCK-8) assay. Cell migration and invasion were assessed by transwell assay. Cell apoptosis was monitored by flow cytometry. The protein levels of epithelial-to-mesenchymal transition (EMT)-related markers and Wnt/β-catenin pathway-related proteins were examined by western blot. Dual-luciferase reporter assay, RNA Immunoprecipitation (RIP) assay or RNA pull-down assay was performed to verify the interaction among circ_0067934, miR-1182 and KLF8. Xenograft assay was used to detect tumor growth in vivo. We found that circ_0067934 and KLF8 were up-regulated, while miR-1182 was down-regulated in NSCLC tissues and cells. Circ_0067934 knockdown blocked proliferation, migration, invasion and EMT and induced apoptosis in NSCLC cells. Circ_0067934 regulated NSCLC progression by sponging miR-1182. MiR-1182 targeted KLF8 to hinder NSCLC development. In addition, depletion of circ_0067934 restrained tumor growth in vivo. In conclusion, Circ_0067934 acted as a competing endogenous RNA to facilitate NSCLC progression by regulating the miR-1182/KLF8 axis and activating Wnt/β-catenin pathway.

Zhao M ，Ma W ，Ma C 《-》

Circ_0006988 promotes the proliferation, metastasis and angiogenesis of non-small cell lung cancer cells by modulating miR-491-5p/MAP3K3 axis.

Yang C ，Shi J ，Wang J ，Hao D ，An J ，Jiang J ... -  《-》

Circular RNA circ_0003028 contributes to tumorigenesis by regulating GOT2 via miR-1298-5p in non-small cell lung cancer.

Guan H ，Sun C ，Gu Y ，Li J ，Ji J ，Zhu Y ... -  《-》

Exosomal circ_PIP5K1A regulates the progression of non-small cell lung cancer and cisplatin sensitivity by miR-101/ABCC1 axis.

Shao N ，Song L ，Sun X 《-》

Circ_0072088 promotes the development of non-small cell lung cancer via the miR-377-5p/NOVA2 axis.

Non-small cell lung cancer (NSCLC) is one of the leading causes of cancer-related death globally. This study aimed to disclose the role of circular RNA circ_0072088 in NSCLC and illustrate its potential mechanism. Quantitative real-time polymerase chain reaction (qRT-PCR) was applied to detect the expression of circ_0072088, zinc finger RNA binding protein (ZFR), microRNA-377-5p (miR-377-5p) and NOVA alternative splicing regulator 2 (NOVA2). The viability, colony formation, cell cycle, migration and invasion of NSCLC cells were measured by cell counting kit-8 (CCK8) assay, colony formation assay, flow cytometry, wound healing assay and transwell invasion assay. Western blot assay was employed to examine the protein levels of proliferating cell nuclear antigen (PCNA), Cyclin D1, matrix metallopeptidase 2 (MMP2), MMP9 and NOVA2. The downstream targets of circ_0072088 and miR-377-5p were searched through using circular RNA Interactome and TargetScan databases, and the interaction between miR-377-5p and circ_0072088 or NOVA2 was confirmed by dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay. in vivo tumor growth assay was used to evaluate the functions of circ_0072088 in the progression of NSCLC in vivo. GSE101586 dataset and the analysis of tissue specimens showed that circ_0072088 was aberrantly upregulated in tumor tissues of lung cancer and NSCLC. Circ_0072088 interference caused marked suppression on the proliferation and motility of NSCLC cells. Circ_0072088 could negatively regulate miR-377-5p through direct combination. Circ_0072088 contributed to the progression of NSCLC through sponging miR-377-5p. MiR-377-5p could directly interact with NOVA2, and the overexpression of NOVA2 overturned miR-377-5p-mediated influence on NSCLC cells. Circ_0072088 facilitated the progression of NSCLC in vivo. Circ_0072088 facilitated the proliferation and metastasis of NSCLC cells through upregulating NOVA2 via functioning as a competitive endogenous RNA (ceRNA) for miR-377-5p.

Tan Z ，Cao F ，Jia B ，Xia L ... -  《-》