Circ_0000003 promotes the proliferation and metastasis of non-small cell lung cancer cells via miR-338-3p/insulin receptor substrate 2

Abstract

Background: Circular RNAs (circRNAs) play a pivotal regulatory role in a variety of tumors. Nevertheless, the detailed function of circ_0000003 in non-small cell lung cancer (NSCLC) and its regulatory mechanism remain elusive. Methods: RT-PCR was carried out to detect the expressions of circ_0000003, miR-338-3p and insulin receptor substrate 2 (IRS2)in NSCLC tissues. Besides, western blot was done to monitor IRS2 expression in NSCLC cells. The correlation between circ_0000003 and clinicopathologic characteristics of NSCLC patients was analyzed as well.CCK8 and BrdUassays were used to monitor cell proliferation; flow cytometry was used to detect apoptosis; and transwell assay was conducted to detect its migration and invasion.Moreover, dual luciferase reporter gene assay was done to verify the targeting relationship between circ_0000003 and miR-338-3p.Additionally, the effect of circ_0000003 on the growth of NSCLC cells in vivo was evaluated by tumorigenesis assay in nude mice. Results: The expression of circ_0000003 was significantly high in NSCLC tissues and cell lines, and its high expression level was notably correlated with lymph node metastasis andTNM staging.In vitro experiments showed that overexpression of circ_0000003 facilitated the proliferation, migration, invasion and inhibited the apoptosis of NSCLC cells, while the knockdown of circ_0000003 had the opposite effect.In vivo experiments revealed that knockdown of circ_0000003 impeded tumor growth and metastasis. Further, the underlying mechanism showed that circ_0000003 functioned as endogenous competitive RNA and directly targeted miR-338-3p to positively regulated IRS2 expression. Conclusion: Circ_0000003 promotes the proliferation and metastasis of NSCLC cells via modulating miR-338-3p/IRS2 axis.

linc00968 inhibits the tumorigenesis and metastasis of lung adenocarcinoma via serving as a ceRNA against miR-9-5p and increasing CPEB3

“…Lung cancer is the major cause of cancer-associated death worldwide. Nearly 80% of lung cancer diagnoses are non-small-cell lung cancer (NSCLC) and the major subtypes are lung squamous cell carcinoma (LSCC) and lung adenocarcinoma (LUAD) [ 1 ]. Despite the great advances in the diagnostics, targeted drugs and immunotherapy, the overall survival (OS) remains unsatisfactory for patients with NSCLC owing to patients diagnosed with NSCLC had cancer cell diffusion and metastases [ 2 ].…”

A Network Pharmacology Approach to Investigate the Anticancer Mechanism and Potential Active Ingredients of Rheum palmatum L. Against Lung Cancer via Induction of Apoptosis

“…found that patients with non-small cell lung cancer (NSCLC) would further develop resistance to the available treatments by activating insulin-like growth factor-1 receptor (IGF1R) ( Hayakawa et al., 2020 ). In addition, it’s reported that INS plays an important role in the proliferation and metastasis of NSCLC cells ( Li S. et al., 2019 ). AKT is an important kinase in the PI3k-AKT pathway, which is catalyzed by PI3K to migrate to the cell membrane and activate ( Zhang et al., 2019 ).…”

CircHIPK3/miR-381-3p axis modulates proliferation, migration, and glycolysis of lung cancer cells by regulating the AKT/mTOR signaling pathway

“…There are still some limitations to this project. CeRNA network circRNA/miRNA/mRNA in lung cancer was widely identified [ 6 , 7 , 32 , 33 ]. Therefore, the downstream mRNA of the circHIPK3/miR-381-3p axis is worthy of further exploration to enrich our cognition on the mechanism of circHIPK3 in lung cancer.…”

“…For instance, circCMPK1 (hsa_circ_0012384) positively modulated cell proliferation of NSCLC cells by increasing cyclin D1 expression by sponging miR-302e [ 6 ]. Li et al reported that circ_0000003 could accelerate the progression of NSCLC by promoting the proliferation and metastasis via the miR-338-3p/IRS2 pathway [ 7 ]. Gao and his colleagues alleged that hsa_circ_0007059 inhibited lung cancer cell growth and epithelial–mesenchymal transition through the inhibition of miR-378 [ 8 ].…”