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Minerva Medica 2021 Feb 22

DOI: 10.23736/S0026-4806.21.07121-4


language: English

CircTMEM30A/hsa-miR-130a-3p regulates TNFα and promotes the malignant progression of COPD with primary lung cancer

Wenxiao DING 1, Yanbin DONG 2

1 Department of Pulmonary and Critical Care Medicine, ZhongDa Hospital, Medical School, Southeast University, Nanjing, China; 2 Department of Emergency, The First Affiliated Hospital with Nanjing Medical University, Nanjing, China


BACKGROUND: Chronic obstructive pulmonary disease (COPD) and lung cancer is the most common respiratory diseases among smokers. Lung cancer is one of the most common malignancy. COPD patients are at high risk of lung cancer, but the specific pathogenesis is still unclear. In recent years, circRNAs have become the focus of lung cancer research. This study investigated the effect of CircTMEM30A on COPD and lung cancer and its possible molecular mechanisms.
METHODS: QPCR was used to detect the expression of CircTMEM30A in COPD patients, lung cancer patients, and COPD patients with lung cancer. CircTMEM30A was transfected with PPF, HFL1, A549 and NCI-H446 cells, and the transfection efficiency was verified by real-time quantitative PCR. The effects of CircTMEM30A on the proliferation, migration and invasion of fibroblasts and lung cancer cells were detected by MTT, Transwell and scratch tests. The target gene of CircTMEM30A was verified by luciferase reporter assay. Real-time quantitative PCR was used to detect the expression level of CircTMEM30A target gene.
RESULTS: CircTMEM30A was the most highly expressed in COPD patients with lung cancer. Overexpression of CircTMEM30A enhanced the effects of proliferation, migration and invasion of fibroblasts and lung cancer cells, down-regulated the expression of E-cadherin, up-regulated the expression of Vimentin, and promoted EMT. After knocking down CircTMEM30A, the migration and invasion ability of lung cancer cells was significantly reduced. Bioinformatics retrieval and luciferase reporter gene confirmed that CircTMEM30A could be bind to miR-130a, while TNFα gene was the target gene of miR-130a. Further studies showed that overexpression of miR-130a and knockdown of TNFα reversed the promoting effect of CircTMEM30A on lung cancer cells.
CONCLUSIONS: CircTMEM30A was highly expressed in COPD patients with lung cancer, and miR-130a was low expressed in lung cancer cells. CircTMEM30A regulated the expression of TNFα through miR-130a, thereby affecting the progression of COPD and lung cancer. CircTMEM30A may be a therapeutic target for COPD patients with lung cancer.

KEY WORDS: Chronic obstructive pulmonary disease; Primary lung cancer; CircTMEM30A; hsa-miR-130a-3p; TNFα

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