Matrine Regulates Proliferation, Apoptosis, Cell Cycle, Migration, and Invasion of Non-Small Cell Lung Cancer Cells Through the circFUT8/miR-944/YES1 Axis

Abstract

Background: Non-small cell lung carcinoma (NSCLC) is the major histological subtype of cancer cases. In the present study, we investigated the association between Matrine, an active component of Chinese medicine, and circFUT8 in NSCLC cells. Methods: The proliferation ability of NSCLC cells was assessed by MTT and colonyforming assays. Flow cytometry assay was performed to show the apoptosis and cell cycle distribution in NSCLC cells. The protein expression levels of Bcl-2, Cleaved Caspase-3 (C-Caspase3), and YES proto-oncogene 1 (YES1) were measured by Western blot assay. Migration and invasion of NSCLC cells were determined by transwell assay. The expression levels of circFUT8, miR-944 and YES1 were quantified by real-time quantitative polymerase chain reaction (RT-qPCR) assay. The interaction relationship between miR-944 and circFUT8 or YES1 was confirmed by dual-luciferase reporter assay. The anti-tumor role of Matrine in vivo was explored by a xenograft experiment. Results: Matrine functioned as a carcinoma inhibitor by repressing proliferation, cell cycle process, migration, and invasion while inducing apoptosis in NSCLC cells. Importantly, overexpression of circFUT8 counteracted Matrine-induced effects on NSCLC cells. MiR-944, interacted with YES1, was a target of circFUT8. Under Matrine condition, overexpression of circFUT8 increased proliferation, migration, and invasion while inhibited apoptosis, which was abolished by the upregulation of miR-944. Whereas the silencing of YES1 counteracted miR-944 inhibitor-induced effects on NSCLC cells. Eventually, we also confirmed that Matrine impeded NSCLC tumor growth in vivo. Conclusion: Matrine regulated proliferation, apoptosis, cell cycle, migration, and invasion of NSCLC cells through the circFUT8/miR-944/YES1 axis, which provided novel information for Matrine in NSCLC.

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

“…Furtherly analysis suggested that the downregulation of miR-1298-5p could partly abolish the repression role of circ_0003028 knockdown on NSCLC progression. Additionally, circ_0003028 was reported to partake in the regulation of cell growth and metastasis in liver cancer and NSCLC by sponging multiple miRNAs [ 13 , 32 ]. These results inducted that circ_0003028 involves in complex regulatory networks.…”

Digital multiplexed analysis of circular RNAs in FFPE and fresh non‐small cell lung cancer specimens

“…Hsa-miR-186 was described downregulated in NSCLC, acting as an inhibitor of cancer proliferation, progression, and metastasis [40,41], whereas hsa-miR-1305 was not described in any type of cancer thus far. Another mechanism of action of circFUT8 in NSCLC has been described by Zhu et al [42] in a recent publication, where this circRNA was shown to increase proliferation, invasion, and migration of NSCLC cells via miR-944/YESI axis.…”

“…Another mechanism of action of circFUT8 in NSCLC has been described by Zhu et al. [ 42 ] in a recent publication, where this circRNA was shown to increase proliferation, invasion, and migration of NSCLC cells via miR‐944/YESI axis.…”

CRISPR/Cas9 application in cancer therapy: a pioneering genome editing tool

“…YES1 adjusts cell growth, survival, apoptosis, cell–cell adhesion, and cytoskeleton remodeling. Its levels have been found to be enhanced in patients with lung cancer, making it a potential therapeutic target in lung cancer [ 167 ]. The vital role of YES1 in lung carcinogenesis was revealed by its obstruction using the CRISPR/Cas9 system, leading to disrupted growth and metastasis of NSCLC by downregulation of mTOR signaling, a positive regulator of carcinogenesis [ 168 ].…”