H19 promotes non‐small‐cell lung cancer (NSCLC) development through STAT3 signaling via sponging miR‐17

Huang, Zhiwen; Lei, Wei; Hu, Haibo; Zhang, Hongyan; Zhu, Yehan

doi:10.1002/jcp.26530

Cited by 90 publications

(63 citation statements)

References 45 publications

(53 reference statements)

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“…The roles of lncRNAs in cancer progression have long been researched and H19 was widely accepted as an oncogene in cancers, including NSCLC ( 27 ). However, its role in gefitinib resistance is not well known.…”

Section: Discussionmentioning

confidence: 99%

Tumor‑released lncRNA H19 promotes gefitinib resistance via packaging into exosomes in non‑small cell lung cancer

et al. 2018

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Currently, resistance to tyrosine kinase inhibitors, such as gefitinib, has become one major obstacle for improving the clinical outcome of patients with metastatic and advanced-stage non-small cell lung cancer (NSCLC). While cell behavior can be modulated by long non-coding RNAs (lncRNAs), the contributions of lncRNAs within extracellular vesicles (exosomes) are largely unknown. To this end, the involvement and regulatory functions of lncRNA H19 wrapped by exosomes during formation of gefitinib resistance in human NSCLC were investigated. Gefitinib-resistant cell lines were built by continuously grafting HCC827 and HCC4006 cells into gefitinib-contained culture medium. RT-qPCR assays indicated that H19 was increased in gefitinib-resistant cells when compared to sensitive parent cells. Functional experiments revealed that silencing of H19 potently promoted gefitinib-induced cell cytotoxicity. H19 was secreted by packaging into exosomes and this packaging process was specifically mediated by hnRNPA2B1. H19 wrapped in exosomes could be transferred to non-resistant cells, thus inducing gefitinib resistance. Moreover, treatment-sensitive cells with exosomes highly-expressing H19 induced gefitinib resistance, while knockdown of H19 abrogated this effect. In conclusion, H19 promoted gefitinib resistance of NSCLC cells by packaging into exosomes. Therefore, exosomal H19 may be a promising therapeutic target for EGFR+ NSCLC patients.

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Section: Discussionmentioning

confidence: 99%

Tumor‑released lncRNA H19 promotes gefitinib resistance via packaging into exosomes in non‑small cell lung cancer

et al. 2018

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“…H19 is transcribed exclusively from the maternal allele, and the gene also generates an oncofetal RNA that is expressed in the developing embryo and in certain types of tumor [ 11 , 12 ]. Recent evidence indicates that H19 enhances invasion and metastasis in bladder cancer [ 13 , 14 ], glioma [ 15 ], osteosarcoma [ 16 ], acute myeloid leukemia [ 17 ], breast cancer [ 18 , 19 ], non-small cell lung cancer [ 20 ], gastric cancer [ 21 ], and pancreatic cancer [ 22 ], but suppresses the aggressiveness of hepatocellular carcinoma [ 23 ] and prostate cancer [ 24 ].…”

Section: Introductionmentioning

confidence: 99%

H19 long non-coding RNA contributes to sphere formation and invasion through regulation of CD24 and integrin expression in pancreatic cancer cells

et al. 2018

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The long non-coding RNA H19 is highly expressed in several cancers, and the functions of H19 vary among cancer cell types. Recently, we reported that H19 contributes to the metastasis of pancreatic ductal adenocarcinoma (PDAC) cells and that inhibition of H19 reduces metastasis in vivo. However, the molecular mechanisms underlying the metastasis-promoting role of H19 in PDAC cells remain poorly elucidated. In this study, we clarified the mechanisms by which H19 regulates PDAC metastasis, with a focus on cancer stem cells (CSCs), by using H19-overexpressing and knockdown PDAC cells. Whereas the sphere-formation and invasion abilities of PDAC cells depended on H19 expression levels, other CSC characteristics of the cells, including stemness-marker expression and anticancer-drug resistance, were unaffected by H19 levels. Furthermore, metalloproteinase activity, a key mediator of invasion, was also independent of H19 expression. By contrast, H19 promoted cell adhesion through regulation of integrin and CD24 expression. Notably, the increased adhesion of H19-overexpressing cells was blocked by an anti-β1-integrin antibody, and this resulted in the inhibition of sphere formation and invasion. Thus, H19 plays critical roles in the CSC self-renewal and cell adhesion of PDAC that lead to invasion and metastasis. Our findings suggest that H19 represents a novel therapeutic target for the metastasis of pancreatic cancer.

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“…lncRNAs are divided into carcinogenic lncRNAs and tumor suppressor lncRNAs. As with other tumor types, such as colon cancer and liver cancer (6), the upregulation of carcinogenic lncRNAs in NSCLC can enhance cell proliferation as well as the migratory and invasive capacity, and reduce tumor cell apoptosis and tumor drug sensitivity, including MALAT1, HOTAIR and AFAP1 (13)(14)(15)(16)(17). Recently, numerous carcinogenic lncRNAs have been discovered in NSCLC, including HOTAIR, MALAT1, colon cancer associated transcript 2, H19 imprinted maternally expressed transcript and AFAP1 antisense RNA 1 (13)(14)(15)(16)(17), whereas SPRY4 intronic transcript 1, maternally expressed 3, GAS6 antisense RNA 1, growth arrest specific 5 and promoter of CDKN1A antisense DNA damage activated RNA PANDAR have been reported as tumor suppressor lncRNAs in NSCLC (18)(19)(20)(21)(22).…”

Section: Discussionmentioning

confidence: 99%

LINC00210 plays oncogenic roles in non‑small cell lung cancer by sponging microRNA‑328‑5p

Liu

Zhang

et al. 2020

Exp Ther Med

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Long noncoding RNA (lncRNA) has an important role in regulating non-small cell lung cancer (NSCLC) progression. The present study aimed to investigate the effect of LINC00210 in NSCLC progression in order to provide a novel treatment target for patients with NSCLC. A total of 39 NSCLC patients were obtained and divided into LINC00210 high expression and low expression groups. Subsequently, the 5-year survival rate from this patient cohort was analyzed. The SK-MES-1 and A549 NSCLC and the human 16-HBE bronchial epithelial cell lines were utilized to investigate expression level of LIN00210. A549 cells were used to investigate cell proliferation, migration and invasive abilities using Cell Counting kit 8, Transwell and Matrigel assays, respectively. In addition, the luciferase reporter gene assay was performed to investigate the potential target of LINC00210. Reverse transcription-quantitative PCR was used to determine LINC00210 and microRNA (miR)-328-5p expression levels in NSCLC tissues and tumor cell lines (SK-MES-1 and A549). The results demonstrated that LINC00210 was upregulated in NSCLC tissues and cell lines compared with that in normal tissues and 16-HBE cells, and that LINC00210 expression was associated with a poor prognosis in patients with NSCLC (P<0.05). Furthermore, A549 cell transfection with small interfering (si)LINC00210#1 and siLINC00210#2 induced a significant decrease in cell proliferation, and migratory and invasive abilities compared with that in the control groups (P<0.05). In addition, miR-328-5p overexpression was stimulated by knockdown of LINC00210. Furthermore, A549 cells transfected with siLINC00210#1 and miR-328-5p inhibitor exhibited a significant increase in cell proliferation, and migratory and invasive ability compared with that in A549 cells transfected with siLINC00210#1. These findings suggest that LINC00210 may serve as an oncogenic role in NSCLC by sponging miR-328-5p.

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H19 promotes non‐small‐cell lung cancer (NSCLC) development through STAT3 signaling via sponging miR‐17

Cited by 90 publications

References 45 publications

Tumor‑released lncRNA H19 promotes gefitinib resistance via packaging into exosomes in non‑small cell lung cancer

Tumor‑released lncRNA H19 promotes gefitinib resistance via packaging into exosomes in non‑small cell lung cancer

H19 long non-coding RNA contributes to sphere formation and invasion through regulation of CD24 and integrin expression in pancreatic cancer cells

LINC00210 plays oncogenic roles in non‑small cell lung cancer by sponging microRNA‑328‑5p

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