Dataset Information

Downregulation of circATXN7 represses non-small cell lung cancer growth by releasing miR-7-5p.

ABSTRACT:

Background

Circular RNAs (circRNAs) participate in the occurrence and progression of many cancers. CircRNA ataxin 7 (circATXN7) (circBase ID: hsa_circ_0066436) plays a promoting influence on gastric cancer progression. However, the biological role of circATXN7 in non-small cell lung cancer (NSCLC) is indistinct.

Methods

Levels of circATXN7, microRNA (miR)-7-5p, and profilin 2 (PFN2) mRNA were detected using quantitative real-time polymerase chain reaction (RT-qPCR). Proliferation, apoptosis, metastasis, and invasion were analyzed using cell counting kit-8 (CCK-8), colony formation, 5-ethynyl-2'-deoxyuridine (EdU), flow cytometry, and transwell assays. Protein levels were analyzed using western blotting (WB) and immunohistochemistry (IHC). The relationship between circATXN7 or PFN2 and miR-7-5p was analyzed by dual-luciferase reporter and RNA immunoprecipitation (RIP) assays. The biological function of circATXN7 was verified by xenograft assay.

Results

CircATXN7 and PFN2 were highly expressed in NSCLC, whereas miR-7-5p expression had the opposite trend. CircATXN7 overexpression constrained apoptosis and promoted proliferation, metastasis, invasion, and epithelial-mesenchymal transition of NSCLC cells, but circATXN7 silencing played the opposing influence and repressed xenograft tumor growth in vivo. CircATXN7 served as a miR-7-5p sponge, and circATXN7 regulated malignant behaviors of NSCLC cells through sponging miR-7-5p. PFN2 acted as a miR-7-5p target. PFN2 silencing overturned the promoting effect of miR-7-5p inhibitor on NSCLC cell malignancy, while PFN2 overexpression reversed the inhibitory impact of miR-7-5p mimic on NSCLC cell malignancy.

Conclusion

CircATXN7 accelerated the malignancy of NSCLC cells through adsorbing miR-7-5p and upregulating PFN2, offering evidence to support circATXN7 as a target for NSCLC treatment.

SUBMITTER: Li D

PROVIDER: S-EPMC9161317 | biostudies-literature | 2022 Jun

REPOSITORIES: biostudies-literature

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Publications

Downregulation of circATXN7 represses non-small cell lung cancer growth by releasing miR-7-5p.

Li Dongliang D Fu Zejun Z Dong Chaoqun C Song Yongming Y

Thoracic cancer 20220421 11

<h4>Background</h4>Circular RNAs (circRNAs) participate in the occurrence and progression of many cancers. CircRNA ataxin 7 (circATXN7) (circBase ID: hsa_circ_0066436) plays a promoting influence on gastric cancer progression. However, the biological role of circATXN7 in non-small cell lung cancer (NSCLC) is indistinct.<h4>Methods</h4>Levels of circATXN7, microRNA (miR)-7-5p, and profilin 2 (PFN2) mRNA were detected using quantitative real-time polymerase chain reaction (RT-qPCR). Proliferation, ...[more]

PMID: 35445786

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Project description:BackgroundLung cancer is a common malignant tumor, with, non-small cell lung cancer (NSCLC) accounting for about 80-85% of cases. This study investigated the expression of miR-137 in NSCLC tissues and cells and its effects on the migration and invasion of NSCLC cells and related mechanisms.MethodsWe collected the neoplastic and paracancerous tissues of NSCLC patients, detected the expression of miR-137 in NSCLC tissues and cell lines by real-time quantitative polymerase chain reaction (RT-qPCR), and analyzed the correlation between miR-137 expression and the clinicopathological features and survival of NSCLC. Following transfection with miR-137 mimic or inhibitor in NSCLC cell lines (A549 or H1299) to upregulate or downregulate the expression of miR-137, transwell assay was employed to detect the effects of miR-137 on migration or invasion. Online software was employed to predict and analyze the target gene of miR-137, and luciferase reporter gene system was adopted to validate it. The effects of miR-137 on the expressions of COX-2 and Epithelial-Mesenchymal Transition (EMT) related proteins were investigated by Western blot.ResultsCompared to paracancerous tissues and BEAS-2B cells, the expressions of miR-137 in NSCLC tissues, A549 and H1299 cells were dramatically down-regulated (P<0.01). After transfection with miR-137 mimic or inhibitor in A549 and H1299 cells, the miR-137 expressions were markedly up-regulated or down-regulated (P<0.01), respectively. The number of migrating or invading cells was observably decreased or increased (P<0.01) after transfected with mimic or inhibitor, respectively, while relative luciferase activity was evidently decreased in cells co-transfected with miR-137 mimic and wild type recombined vector of 3'UTR of COX-2. While the expressions of COX-2 and E-cadherin were both substantially reduced in A549 cells treated with miR-137 mimic, that of vimentin was substantially raised. The expression of miR-137 correlated with smoking history, lymph node metastasis, and TNM clinical stage, and patients with high miR-137 expression had apparent longer survival.ConclusionsThe expression of miR-137 was significantly down-regulated in NSCLC tissues and cells, and correlated with NSCLC progress. miR-137 suppressed the migration and invasion of NSCLC cells through regulating EMT relative proteins by targeting COX-2. miR-137 is expected to become a novel biomarker and therapeutic target of NSCLC.

Dataset Information

Downregulation of circATXN7 represses non-small cell lung cancer growth by releasing miR-7-5p.

Background

Methods

Results

Conclusion

Publications

Downregulation of circATXN7 represses non-small cell lung cancer growth by releasing miR-7-5p.

Similar Datasets

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