LncRNA SNHG16 promotes non‐small cell lung cancer development through regulating EphA2 expression by sponging miR‐520a‐3p

Abstract

Background Recent evidence has found that lncRNA small nucleolar RNA host gene 16 (SNHG16) was associated with cell carcinogenesis in NSCLC. Here, we further investigated the precise functions and mechanisms of SNHG16 in NSCLC progression. Methods The expression of SNHG16, microRNA (miR)‐520a‐3p and EPH Receptor A2 (EphA2) was measured using quantitative real‐time polymerase chain reaction and western blot, respectively. Cell proliferation was determined using 3‐(4, 5)‐dimethylthiahiazo (−z‐y1)‐3, 5‐di‐phenytetrazoliumromide (MTT) assay. The migrated and invaded cells were measured by Transwell assay. Flow cytometry was used to detect apoptotic cells. The interaction between miR‐520a‐3p and SNHG16 or EphA2 was confirmed using a dual‐luciferase reporter assay. Results We found that SNHG16 was upregulated in NSCLC tissues and cell lines, knockdown of SNHG16 inhibited cell proliferation, migration, invasion and induced apoptosis in vitro as well as suppressed tumor growth in vivo. MiR‐520a‐3p directly bound to SNHG16 and miR‐520a‐3p, and SNHG16 acted as a ceRNA in regulating EphA2 through competitively binding to miR‐520a‐3p. Additionally, rescue assay exhibited the anticancer activity mediated by SNHG16 knockdown on NSCLC could be reversed by miR‐520a‐3p inhibition or EphA2 overexpression. Conclusion SNHG16 promoted NSCLC development by regulating the miR‐520a‐3p/EphA2 axis, suggesting novel insights for the pathogenesis of NSCLC and new potential therapeutic targets for the treatment of NSCLC. Key points Knockdown of SNHG16 inhibited NSCLC cell proliferation, migration, invasion and induced apoptosis in vitro as well as suppressed tumor growth in vivo. SNHG16 directly interacted with miR‐520a‐3p. EphA2 was a target of miR‐520a‐3p. SNHG16 could regulate the expression of EphA2 by binding to miR‐520a‐3p. SNHG16 promoted NSCLC development by regulating the miR‐520a‐3p/EphA2 axis.

<p>LncRNA PSMA3-AS1 Promotes Lung Cancer Growth and Invasion via Sponging MiR-4504</p>

“…16,17 For example, lncRNA SNHG16 overexpression promotes proliferation, migration and invasion of lung cancer cells through regulating miR-520a-3p/EphA2 axis. 18 LINC-PINT inhibits lung cancer cell growth, cell cycle, migration and invasion while promoting apoptosis. 19 In addition, lncRNA MIAT upregulation leads to accelerated cell growth and predicts poor prognosis in lung cancer.…”

microRNA-451a promoter methylation regulated by DNMT3B expedites bladder cancer development via the EPHA2/PI3K/AKT axis

“…Promoted EPHA2 expression in cancer cells is linked to a dismal prognosis because of recurrence as a consequence of enhanced metastasis [ 28 ]. As for its upstream miRNAs, EPHA2 has been indicated to be targeted by different miRNAs to participate the development of various cancers, including non-small cell lung cancer [ 29 ], hepatocellular carcinoma [ 30 ] as well as colorectal cancer [ 31 ]. After the validation of the targeting relationship between EPHA2 and miR-451a in BCa cells, we carried out rescue experiments again.…”

LncRNA SNHG16 as a potential biomarker and therapeutic target in human cancers

“…In addition, there are some molecules reported to be mediated by SNHG16, including Stearoyl-CoA Acute Lymphoblastic Leukemia MOLT3 BALB/c nude mice promote [22] Cervical cancer HeLa BALB/c nude mice promote [29] Colorectal cancer LoVo BALB/c nude mice promote [30] Diffuse large B-cell lymphoma OCI-LY7 NOD/SCID mice promote [33] Esophageal squamous cell carcinoma kyse-70 BALB/c nude mice promote [35] Gastric cancer MGC-803 BALB/c nude mice promote [38] Hepatocellular carcinoma HuH7 athymic nude mice inhibit [44] HuH7 BALB/c nude mice promote [47] HepG2 BALB/c nude mice promote [48] HepG2 athymic nude mice promote [49] Hep-3B BALB/c nude mice promote [50] Neuroblastoma SK-N-SH BALB/c nude mice promote [51] Non small cell lung cancer A549 BALB/c nude mice promote [53,54] Oral squamous cell carcinoma TSCCA BALB/c nude mice promote [55] Pancreatic cancer AsPC-1 BALB/c nude mice promote [61] Retinoblastoma Y79 BALB/c nude mice promote [63] Desaturase (SCD) [31], p-AKT and matrix metallopeptidase 9 (MMP9) [60], Dickkopf-related protein 3 (DKK3) [39], and Wnt/β-catenin [36], but the underlying regulate mechanisms are not well uncovered. Furthermore, whether SNHG16 has other regulatory functions still needs further investigation.…”

“…The corresponding AUC values for the lncRNA combination in Ta, T1, and T2-T4 cases were 0.760, 0.827, and 0.878, respectively. In the validation cohort, an AUC for the three-lncRNA combination of 0.826 was obtained, and sensitivity and specificity were let-7b-5p luciferase reporter assay, RIP CDC25B/CDK1 hepatocellular carcinoma [47] miR-124-3p luciferase reporter assay acute Lymphoblastic Leukemia [22] miR-128-3p luciferase reporter assay, RIP HOXA7 neuroblastoma [51] miR-1301 luciferase reporter assay, RNA pull down BCL9 osteosarcoma [59] miR-135a luciferase reporter assay, RIP JAK2/STAT3 gastric Cancer [37] miR-140-5p luciferase reporter assay, RIP, RNA pull down ZEB1 esophageal squamous cell carcinoma [35] luciferase reporter assay, RIP retinoblastoma [63] miR-146a luciferase reporter assay, RIP MUC5AC non small cell lung cancer [53] miR-17-5p luciferase reporter assay TIMP3 bladder cancer [23] luciferase reporter assay, RIP p62 hepatocellular carcinoma [49] miR-186 luciferase reporter assay hepatocellular Carcinoma [50] miR-195 luciferase reporter assay, RIP hepatocellular carcinoma [48] miR-200a-3p luciferase reporter assay colorectal cancer [30] miR-205 ZEB1 osteosarcoma [58] miR-216-5p luciferase reporter assay, RIP, RNA pull down ZEB1 cervical cancer [28] miR-218-5p luciferase reporter assay, RNA pull-down HMGB1 pancreatic cancer [61] miR-302a-3p luciferase reporter assay, RNA pull-down FGF19 hepatocellular carcinoma [46] miR-340 luciferase reporter assay osteosarcoma [56] miR-373 luciferase reporter assay EGFR glioma [43] miR-4518 luciferase reporter assay PRMT5 glioma [41] miR-490-3p luciferase reporter assay HK2 endometrial carcinoma [34] miR-497 luciferase reporter assay BDN, YAP1 papillary thyroid cancer [62] miR-497-5p luciferase reporter assay, RIP, RNA pull down PIM1 diffuse large B-cell lymphoma [33] miR-520a-3p luciferase reporter assay EphA2 non small cell lung cancer [54] miR-628 luciferase reporter assay gastric cancer [40] miR-93 luciferase reporter assay hepatocellular carcinoma [44] miR-98 luciferase reporter assay STAT3 bladder cancer [24] luciferase reporter...…”