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

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.

<p>Long Noncoding RNA LINC01426 Sequesters microRNA-519d-5p to Promote Non-Small Cell Lung Cancer Progression by Increasing ETS1 Expression</p>

“…A bioinformatics analysis revealed a total of 22 miRNAs that were capable of complementary base pairing with LINC01426 ( Figure 3C ). Among these candidates, miR-519d-5p, 29 miR-873-3p, 30 , 31 miR-377-5p, 32 , 33 and miR-548c-3p 34 , 35 were selected for experimental verification because they played critical functions in various human cancers.

Figure 3 LINC01426 is a molecular sponge for miR-519d-5p in NSCLC cells.

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CircASXL1 knockdown represses the progression of colorectal cancer by downregulating GRIK3 expression by sponging miR-1205

“…The small interfering RNAs targeting circASXL1 (si-circASXL1 and si-circASXL1#2), the mimic of miR-1205 (miR-1205 mimic; a chemically synthesized double-stranded mature sequence), the overexpression plasmid of circASXL1 (oe-circASXL1), the inhibitor of miR-1205 (miR-1205 inhibitor; a chemically synthesized double-stranded sequence), the overexpression vector of GRIK3 (pcDNA-GRIK3), the small hairpin RNA against circASXL1 (sh-circASXL1), and respective controls (si-NC, miR-NC mimic, oe-NC, miR-NC inhibitor, pcDNA-NC and sh-NC) were built by Invitrogen Co., Ltd. (Carlsbad, CA, USA). Constructed plasmids or oligonucleotides were transfected into cells using Lipofectamine 2000 (Invitrogen) according to the published methods [ 25 ]. The sequences in this part were displayed in Table S1 .…”

Damage-Associated Molecular Patterns Modulation by microRNA: Relevance on Immunogenic Cell Death and Cancer Treatment Outcome

“…Along this line, the lncRNA TP73-AS1 upregulated HMGB1 expression through sponging miR-142-3p [ 50 ] and also miR-200a-5p [ 56 ]. Finally, the circRNA circ_0007385 enhanced cell proliferation, migration, invasion, and chemoresistance in lung cancer through upregulating miR-519d-3p and thus downregulating HMGB1 [ 79 ].…”