Hsa_circ_0079530/AQP4 Axis Is Related to Non-Small Cell Lung Cancer Development and Radiosensitivity

Abstract

Background: Circular RNAs are associated with non-small cell lung cancer (NSCLC) development and radiosensitivity. Nevertheless, the function and regulation mechanism of hsa_circ_0079530 (circ_0079530) in NSCLC development and radiosensitivity are largely unknown. Methods: The abundances of circ_0079530, microRNA (miR-409-3p), aquaporin 4 (AQP4), E-cadherin, intercellular adhesion molecule-1, vitronectin, proliferating cell nuclear antigen, and matrix metalloproteinase 9 were determined via quantitative reverse transcription polymerase chain reaction or western blotting. Cell proliferation, survival fraction, cycle process, migration, invasion, and in vivo growth were examined by cell counting kit-8, colony formation, flow cytometry, transwell, and xenograft analyses. The binding relationship was assessed via dual-luciferase reporter assay and RNA immunoprecipitation assay. Results: Circ_0079530 expression was increased in NSCLC tissues and radioresistant samples. Circ_0079530 knockdown restrained cell proliferation, migration, and invasion, and facilitated radiosensitivity. Circ_0079530 silence decreased tumor growth with or without radiation treatment. Circ_0079530 was verified as a miR-409-3p sponge, and miR-409-3p downregulation mitigated the effects of circ_0079530 interference on NSCLC cell malignancy and radiosensitivity. AQP4 was directly targeted by miR-409-3p. MiR-409-3p restrained cell proliferation, migration, and invasion, and enhanced radiosensitivity by decreasing AQP4 expression. Notably, circ_0079530 silence decreased AQP4 expression by regulating miR-409-3p expression. Conclusion: Circ_0079530 silence repressed cell proliferation, migration, and invasion, and facilitated radiosensitivity in NSCLC cells by mediating miR-409-3p/AQP4 axis.

Investigating the molecular mechanisms of microRNA‑409‑3p in tumor progression: Towards targeted therapeutics (Review)

“…MiR-409-3p not only exists in tissues and cells but also stably exists in circulating body fluids. For the most part, miR-409-3p acts as a tumor suppressor and was reported to be downregulated in a minimum of 13 cancers, including NSCLC ( 12 , 14 - 17 , 19 - 21 ), BC ( 24 , 26 , 27 , 29 , 30 ), CC ( 31 - 35 ), osteosarcoma ( 36 - 39 ), GC ( 40 - 44 ), CRC ( 45 , 46 , 48 - 51 ), OC ( 53 - 55 ), ccRCC ( 57 , 58 ), BCa ( 59 , 61 ), PTC ( 62 ), AML ( 65 , 66 ), oligodendrogliomas ( 67 ), melanoma ( 68 ), TSCC ( 70 ), glioma ( 79 ), fibrosarcoma ( 81 ) and HCC ( 83 , 84 ). However, miR-409-3p also serves as an oncogene to promote tumor progression.…”

“…In addition to CBR3-AS1, circ_0079530 also had an oncogenic role in NSCLC through the inhibition of miR-409-3p. Yang et al ( 21 ) revealed that the circ_0079530/miR-409-3p/aquaporin 4 ( AQP4 ) axis promoted the proliferation and invasion of H1270 and A549 NSCLC cells.…”

“…A ceRNA named circ_0079530 was overexpressed in NSCLC cells and sequestered miR-409-3p. Increased rates of cell migration and invasion are carried on by low levels of the miRNA, on the contrary, the increase of migration and invasion rate ( 21 ).…”

“…2 ). Furthermore, increasing data point to the broad expression of miR-409-3p in malignancies, particularly non-small cell lung cancer (NSCLC) ( 12 - 21 ), breast cancer (BC) ( 22 - 30 ), cervical cancer (CC) ( 31 - 35 ), osteosarcoma ( 36 - 39 ), gastric cancer (GC) ( 40 - 44 ), colorectal cancer (CRC) ( 45 - 52 ), ovarian cancer (OC) ( 53 - 56 ), renal cell carcinoma (ccRCC) ( 57 , 58 ), bladder cancer (BCa) ( 59 - 61 ), papillary thyroid cancer (PTC) ( 62 ), pancreatic cancer (PC) and biliary tract cancer (BTC) ( 63 ), diffuse large B-cell lymphoma (DLBCL) ( 64 ), acute myeloid leukemia (AML) ( 65 , 66 ), oligodendroglioma ( 67 ), melanoma ( 68 ), nasopharyngeal carcinoma (NPC) ( 69 ), tongue squamous cell carcinoma (TSCC) ( 70 ), prostate cancer (PCa) ( 71 - 76 ), meningioma ( 77 ), intracranial artery tumors ( 78 ), glioma ( 79 , 80 ), fibrosarcoma ( 81 ), glioblastoma ( 82 ) and hepatocellular carcinoma (HCC) ( 83 , 84 ). Specifically, it has been shown that miR-409-3p exerts anti- or pro-tumorigenic roles in cancer progression by targeting downstream mRNAs or modulated by the upstream regulators of long non-coding RNAs (lncRNAs) or circular RNAs (circRNAs).…”

miR-3059-3p Regulates Glioblastoma Multiforme Radiosensitivity Enhancement through the Homologous Recombination Pathway of DNA Repair

“…Several studies have shown that microRNAs can regulate the therapeutic effect of radiation. For example, miR-409-3p mediated radiosensitivity in non-small-cell lung cancer [ 20 ]. miR-31 induced RR by regulating reactive oxygen species in pancreatic ductal adenocarcinoma [ 21 ].…”