Long non-coding RNA HOTTIP promotes BCL-2 expression and induces chemoresistance in small cell lung cancer by sponging miR-216a

Sun, Yanqin; Hu, Bingshuang; Wang, Qiongyao; Ye, Minting; Qiu, Qianqian; Zhou, Yuanyuan; Zeng, Fanrui; Zhang, Xiaomin; Guo, Ying; Guo, Linlang

doi:10.1038/s41419-017-0113-5

Cited by 93 publications

(83 citation statements)

References 30 publications

(39 reference statements)

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“…Increasing evidence indicates that HOTTIP is overexpressed in prostate cancer, lung cancer, and pancreatic cancer . HOTTIP knockdown impedes cell viability, proliferation, invasion, and angiogenesis in human cancer cells, therefore it is been identified as an oncogenic long noncoding RNA (lncRNA).…”

Section: Introductionmentioning

confidence: 99%

Long noncoding RNA HOTTIP mediates SRF expression through sponging miR‐150 in hepatic stellate cells

Zheng

Mao

Dong

et al. 2018

J Cellular Molecular Medi

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HOXA transcript at the distal tip (HOTTIP) has been shown to be up‐regulated in a variety of cancers and is identified as an oncogenic long noncoding RNA. However, the biological role of HOTTIP in liver fibrosis is unclear. Here, we reported that HOTTIP was specifically overexpressed in activated hepatic stellate cells (HSCs). HOTTIP knockdown suppressed the activation and proliferation of HSCs. Luciferase reporter assay showed that HOTTIP and serum response factor (SRF) were targets of miR‐150. RNA binding protein immunoprecipitation assay indicated the interaction between miR‐150 and HOTTIP. Further study revealed that HOTTIP increased SRF expression as a competing endogenous RNA for miR‐150, thus prompting HSC activation. Taken together, we provide a novel HOTTIP‐miR‐150‐SRF signalling cascade in liver fibrosis.

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Section: Introductionmentioning

confidence: 99%

Long noncoding RNA HOTTIP mediates SRF expression through sponging miR‐150 in hepatic stellate cells

Zheng

Mao

Dong

et al. 2018

J Cellular Molecular Medi

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“…Epigenetic mechanisms, which contain DNA methylation, aberrant expression of miRNAs and lncRNAs, ful lled an important role in cancers including but not limited to SCLC (8). Moreover, a growing number of evidences emphasized the contribution of epigenetic alternation of cancer-related ncRNAs to chemotherapy insensitivity (19,20,(28)(29)(30)(31)(32)(33). In the current experiment, we explored the unique methylation patterns of protein-coding and non-coding genes between SCLC patients who experienced PR and patients who were insensitive to the standard chemotherapy.…”

Section: Discussionmentioning

confidence: 99%

“…Mounting evidences investigated the signi cant roles of lncRNAs and miRNAs in chemotherapy insensitivity (26,27). In SCLC drug-resistant cell lines, the aberrant expression of various lncRNAs and miRNAs was found, including lncRNA HOTTIP, lncRNA HOTAIR, miR-92a-2, miR-100, miR-134, miR-137, and miR-147, etc (28)(29)(30)(31)(32)(33).…”

Section: Introductionmentioning

confidence: 99%

Aberrant Methylation Modifications Reflect Specific Drug Responses in Small Cell Lung Cancer

Chen

Guo

Liu

et al. 2020

Preprint

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Background: Epigenetic alterations of specific genes are closely related to chemotherapeutic efficacy in various cancers. However, few comprehensive profiles of differentially methylated genes (DMGs) in small cell lung cancer (SCLC) were available. The current study aimed to explore the association between aberrant methylation modifications of coding and non-coding genes and chemotherapy insensitivity, thus constructing lncRNA-miRNA-mRNA regulatory network in SCLC.Methods: In this study, methylated DNA immunoprecipitation sequencing (MeDIP-Seq) and RNA sequencing (RNA-Seq) was employed to six SCLC patients who were sensitive and insensitive to first-line standard chemotherapy. Then, we verified the therapeutic predictive effects of DMGs in 62 SCLC cell lines and constructed lncRNA-miRNA-mRNA network on the basis of different cohorts and databases. Results: Of 4552 DMGs which were selected (fold change ≥ 2, p<0.01) between chemo-sensitive and chemo-insensitive group, coding genes constituted the largest percentage (3873/4551, 85.08%), followed by lncRNAs (479/4551, 10.52%) and miRNAs (162/4552, 3.56%). Further, both two groups demonstrated two methylation peaks near transcription start site and transcription end site. Two lncRNA-miRNA-mRNA networks which based on genes that showed opposite results in genetic expression and epigenetic modifications suggested the extensive genome connection between chemotherapy efficacy-related non-coding RNAs (ncRNAs) and mRNAs. Combing four DMGs, including hsa-miR-34a, LINC00461, LINC01018, and LINC01484 could effectively predict first-line chemotherapy response in SCLC, indicating that they might play vital roles in SCLC chemotherapy insensitivity. Conclusions: This study was the first to evaluate multiple drugs efficacy-related ncRNAs and mRNAs which were modified by methylation in SCLC. In addition, DMGs identified in our research might serve as predictors for chemotherapy effect and promising therapeutic targets to reverse drugs-insensitivity by complex lncRNA-miRNA-mRNA mechanisms in SCLC. Further comprehensive studies of these findings are worthy of expecting.

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“…Dysregulation of some lncRNAs has been shown in various type of cancers, including lung cancer [18,19]. However, the functions and mechanisms behind antisense lncRNAs in lung cancer remain obscure.…”

Section: Discussionmentioning

confidence: 99%

Long noncoding RNA DPP10-AS1 promotes malignant processes through epigenetically activating its cognate gene DPP10 to predict poor prognosis in lung cancer patients

Tian

Pan

Fang

et al. 2019

Preprint

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Background Long noncoding RNAs (lncRNAs) play oncogenic or tumor-suppressive roles in various cancers. However, the epigenetic modification of lncRNA and its cognate sense gene in lung cancer remain largely unknown.Methods : qRT-PCR and Western blot were conducted to detect the expressions of DDP10-AS1 and DPP10 expression in lung cancer cell lines and tissues. The impact of DDP10-AS1 on DPP10 expression, cell growth, invasion, apoptosis and in vivo tumor growth were investigated in lung cancer cells by Western blot, rescue experiments, colony formation, flow cytometry and xenograft animal experiment.Results A novel antisense lncRNA, DPP10-AS1, is found to be highly expressed in cancer tissues and the upregulation of DPP10-AS1 predicts poor prognosis in lung cancer patients. Notably, DPP10-AS1 promotes lung cancer cell growth, colony formation, cell cycle progression and represses apoptosis in lung cancer cells by upregulating DPP10 expression. Additionally, DPP10-AS1 facilitates lung tumor growth via upregulation of DPP10 protein in xenograft mouse model. Importantly, DPP10-AS1 positively regulates DPP10 gene expression and they are coordinately upregulated in lung cancer tissues. Mechanically, DPP10-AS1 associates with DPP10 mRNA but does not enhance DPP10 mRNA stability. Hypomethylation of DPP10-AS1 and DPP10 contributes to their coordinate upregulation in lung cancer.Conclusions These findings indicate that the upregulated antisense lncRNA DPP10-AS1 promotes lung cancer malignant processes and facilitates tumorigenesis by epigenetically regulating its cognate sense gene DPP10, and DPP10-AS1 may act as a candidate prognostic biomarker and a potential therapeutic target in lung cancer.

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Long non-coding RNA HOTTIP promotes BCL-2 expression and induces chemoresistance in small cell lung cancer by sponging miR-216a

Cited by 93 publications

References 30 publications

Long noncoding RNA HOTTIP mediates SRF expression through sponging miR‐150 in hepatic stellate cells

Long noncoding RNA HOTTIP mediates SRF expression through sponging miR‐150 in hepatic stellate cells

Aberrant Methylation Modifications Reflect Specific Drug Responses in Small Cell Lung Cancer

Long noncoding RNA DPP10-AS1 promotes malignant processes through epigenetically activating its cognate gene DPP10 to predict poor prognosis in lung cancer patients

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