circ _0007385 served as competing endogenous RNA for miR ‐519d‐3p to suppress malignant behaviors and cisplatin resistance of non‐small cell lung cancer cells
Authors: Yinghong Li
Yancheng Ye
Caixia Xi
Qingke Li
Zhengguo Li
Liangcun Zhao
Journal: Thoracic Cancer (2020)
Discipline: CLINICAL MEDICINE
Keywords: HMGB1; NSCLC; circ_0007385; miR-519d-3p.
Affiliations: Department of Pharmacy, Gansu Wuwei Tumor Hospital, Wuwei, China., Department of Laboratory medicine, Gansu Wuwei Tumor Hospital, Wuwei, China., Department of Respiratory Medicine, Gansu Wuwei Tumor Hospital, Wuwei, China., Department of Integrated Traditional Chinese and Western Medicine, Gansu Wuwei Tumor Hospital, Wuwei, China.

Abstract:  Background: Circular RNAs (circRNAs) have been closely implicated in competing endogenous RNA (ceRNA) network among human cancers including non-small cell lung cancer (NSCLC). However, the role of most circRNAs in NSCLC remains to be determined. Here, we aimed to investigate the role of hsa_circ_0007385 (circ_0007385) in NSCLC cells. Methods: Expression of hsa_circ_0007385 (circ_0007385), miRNA (miR)-519d-5p and high-mobility group box 1 (HMGB1) was measured by real-time quantitative PCR and western blotting. Functional experiments were evaluated by cell counting kit (CCK)-8, flow cytometry, fluorescein active caspase-3 staining kit, transwell assays, western blotting, and xenograft experiment. The relationship among circ_0007385,miR-519d-5p and HMGB1 was testified by dual-luciferase reporter assay. Kaplan-Meiersurvival curve identified overall survival in NSCLC patients. Results: circ_0007385 expression was higher in NSCLC tissues and cell lines, and was associated with poor overall survival. Silencing circ_0007385 could suppress cell proliferation, migration and invasion in A549 and H1975 cells, as well as cisplatin (DDP) resistance. Moreover, circ_0007385 silence retarded tumor growth of A549 cells in vivo. Molecularly, there was a direct interaction between miR-519d-3p and either circ_0007385 or HMGB1; expression of miR-519d-3p was downregulated in NSCLC tumors in a circ_0007385-correlated manner, and circ_0007385 could indirectly regulate HMGB1 via miR-519d-3p. Functionally, both inhibiting miR-519d-3p and restoring HMGB1 could overturn the suppressive effect of circ_0007385 knockdown on cell proliferation, migration, invasion, and DDP resistance. Conclusions: Collectively, circ_0007385 deletion could function anti-tumor role in NSCLC by suppressing malignant behaviors and DDP resistance in vitro and in vivo via circ_0007385/miR-519d-3p/HMGB1 axis. These outcomes might enhance our understanding of the molecular mechanisms underlying the malignant progression of NSCLC. Key points: SIGNIFICANT FINDINGS OF THE STUDY: circ_0007385 was upregulated in NSCLC tissues and cells, and was associated with poor overall survival. Silenced circ_0007385 suppressed NSCLC cell proliferation, migration, invasion, and DDP resistance in vitro, and tumor growth in vivo. circ_0007385 was upregulated in NSCLC tissues and cells, and was associated with poor overall survival. What this study adds: miR-519d-3p could directly interact with circ_0007385 and HMGB1 in NSCLC cells. A promising circ_0007385/miR-519d-3p/HMGB1 regulatory pathway was determined in NSCLC cells. 

Retracted: No

PubPeer comments:
 Figs 3c d,  Flow cytometry (FCM) and Annexin V fluorescein isothiocyanate (FITC) apoptosis detection kit examined apoptosis rate (%) after treatment of 10 u03bcM of DDP. ![file] Similar in style to Figs 2G H of [Qiu et al (2021)] ,  The apoptotic rate was determined by flow cytometry . **[Retracted]** ![] Fig 2G of [Jiang et al (2020)] **[retracted on authors request]** ![] Fig 2C of [Gong Zhu (2020)] **[retracted for papermill origins]**. ![] ,