Long noncoding RNA HOXD‐AS2 regulates cell cycle to promote glioma progression

Qi, Yingjiao; Wang, Zhixing; Wu, Fan; Yin, Bin; Jiang, Tao; Qiang, Boqin; Yuan, Jing; Han, Wei; Peng, Xiaozhong

doi:10.1002/jcb.28117

Cited by 20 publications

(24 citation statements)

References 24 publications

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“…For example, LINC01123 is upregulated in intrahepatic cholangiocarcinomas (64) and is associated with poor prognosis in prostate cancer (65). Similarly, HOXD-AS2 is upregulated in glioma cells and is associated with poor prognosis (66). Consistent with these previous studies, the present study revealed that LINC01123 and HOXD-AS2 were upregulated in numerous types of cancer and were associated with reduced patient OS time.…”

Section: Discussionsupporting

confidence: 90%

A putative competing endogenous RNA network in cisplatin‑resistant lung adenocarcinoma cells identifying potentially rewarding research targets

Huang

Wei

et al. 2020

Oncol Lett

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Lung adenocarcinoma (LUAD) is the most common type of non-small cell lung cancer and has a poor 5 year survival rate (<10%). Cisplatin is one of the most effective chemotherapeutic treatments for LUAD, even though it is of limited overall utility due to acquired drug resistance. To identify possible genetic targets for the mitigation of cisplatin resistance, gene expression data from cisplatin-resistant cell lines were integrated with patient information. Expression data for cisplatin-resistant and cisplatin-sensitive A549 cell lines were obtained from the Gene Expression Omnibus database, while LUAD patient data was obtained from The Cancer Genome Atlas (TCGA) database. Differentially expressed mRNAs (DEmRNAs), microRNAs (DEmiRNAs) and long non-coding RNAs (DElncRNAs) were identified between the cisplatin-sensitive and cisplatin-resistant cells. Using the TCGA patient data, 33 DEmRNAs associated with survival were identified. A total of 74 DElncRNAs co-expressed with the survival-associated DEmRNAs, and 11 DEmiRNAs that regulated the survival-associated DEmRNAs, were also identified. A competing endogenous RNA (ceRNA) network was constructed based on the aforementioned results, which included 17 survival-associated DEmRNAs, 9 DEmiRNAs and 16 DElncRNAs. This network revealed 8 ceRNA pathway axes possibly associated with cisplatin resistance in A549 cells. Specifically, the network suggested that the lncRNAs HOXD-AS2, LINC01123 and FIRRE may act as ceRNAs to increase cisplatin resistance in human LUAD cells. Therefore, it was speculated that these lncRNAs represent potentially rewarding research targets.

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Section: Discussionsupporting

confidence: 90%

A putative competing endogenous RNA network in cisplatin‑resistant lung adenocarcinoma cells identifying potentially rewarding research targets

Huang

Wei

et al. 2020

Oncol Lett

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“… 26 GBM patients with high HOXD-AS2 levels experience significantly shorter overall survival times. 27 Using catRAPID, 28 we revealed the predicted binding between KSRP and the 3′ end of HOXD-AS2 with a high discriminative power ( Supplementary Figure 11 ). Ectopic expression of HOXD-AS2 rescued TMZ-induced increases in apoptosis ( Supplementary Figure 12A ), whereas it decreased γ-H2AX and cleaved caspase-3 levels ( Supplementary Figure 12B ).…”

Section: Resultsmentioning

confidence: 99%

TGF-β1 modulates temozolomide resistance in glioblastoma via altered microRNA processing and elevated MGMT

et al. 2020

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Background Our previous studies have indicated that miR-198 reduces cellular methylguanine DNA methyltransferase (MGMT) levels to enhance temozolomide sensitivity. Transforming growth factor beta 1 (TGF-β1) switches off miR-198 expression by repressing K-homology splicing regulatory protein (KSRP) expression in epidermal keratinocytes. However, the underlying role of TGF-β1 in temozolomide resistance has remained unknown. Methods The distribution of KSRP was detected by Western blotting and immunofluorescence. Microarray analysis was used to compare the levels of long non-coding RNAs (lncRNAs) between TGF-β1–treated and untreated cells. RNA immunoprecipitation was performed to verify the relationship between RNAs and KSRP. Flow cytometry and orthotopic and subcutaneous xenograft tumor models were used to determine the function of TGF-β1 in temozolomide resistance. Results Overexpression of TGF-β1 contributed to temozolomide resistance in MGMT-promoter hypomethylated glioblastoma cells in vitro and in vivo. TGF-β1 treatment reduced cellular MGMT levels through suppressing the expression of miR-198. However, TGF-β1 upregulation did not affect KSRP expression in glioma cells. We identified and characterized two lncRNAs (H19 and HOXD-AS2) that were upregulated by TGF-β1 through SMAD signaling. H19 and HOXD-AS2 exhibited competitive binding to KSRP and prevented KSRP from binding to pri-miR-198, thus decreasing miR-198 expression. HOXD-AS2 or H19 upregulation strongly promoted temozolomide resistance and MGMT expression. Moreover, KSRP depletion abrogated the effects of TGF-β1 and lncRNAs on miR-198 and MGMT. Finally, we found that patients with low-levels of TGF-β1 or lncRNA expression benefited from temozolomide therapy. Conclusions Our results reveal an underlying mechanism by which TGF-β1 confers temozolomide resistance. Furthermore, our findings suggest that a novel combination of temozolomide with a TGF-β inhibitor may serve as an effective therapy for glioblastomas.

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“…Some researchers have demonstrated that lncRNAs participated in the progression of gliomas. For instance, a paper from Qi Y et al, reported that lncRNA HOXD-AS2 promoted the progression of gliomas and might act as a promising target for the diagnosis and therapy of gliomas [10]. In addition, lncRNA MT1JP inhibits the proliferation, invasion and migration of glioma cells by activating the PTEN/Akt signaling pathway [11].…”

Section: Introductionmentioning

confidence: 99%

Expression and prognostic value of long non-coding RNA H19 in glioma via integrated bioinformatics analyses

Xiao

Zhu

Jian-xiong

et al. 2020

Aging

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Numerous discoveries have elucidated that long noncoding RNAs (lncRNAs) play a critical role in cancer malignant progression. However, their potential involvement in gliomas remains to be explored. Herein, the expression level of lncRNA H19 in glioma tissues, and its relevance with clinical characteristics were analyzed through Oncomine. The results showed that H19 was highly expressed in glioma tissues and its expression increased with the increase of malignancy. Next, GTEx and TCGA data were downloaded for differently expressed genes (DEGs) identification, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses, and the correlation analyses between H19 expression and clinic features. Radiation therapy had a good effect on glioblastoma multiforme (GBM), but didn't have a good effect on low grade glioma (LGG). Meanwhile, the expression level of H19 could act as an indicator molecule indicating the effect of radiotherapy. Finally, gene set enrichment analysis (GSEA) and immune infiltration analysis were conducted. It was found that H19 could affect the immune infiltration level of glioma through copy number variations, thus affecting the prognosis of glioma patients. Collectively, H19 may be involved in the occurrence and development of glioma, and has potential reference value for the relief and immunotherapy of glioma.

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Long noncoding RNA HOXD‐AS2 regulates cell cycle to promote glioma progression

Cited by 20 publications

References 24 publications

A putative competing endogenous RNA network in cisplatin‑resistant lung adenocarcinoma cells identifying potentially rewarding research targets

A putative competing endogenous RNA network in cisplatin‑resistant lung adenocarcinoma cells identifying potentially rewarding research targets

TGF-β1 modulates temozolomide resistance in glioblastoma via altered microRNA processing and elevated MGMT

Expression and prognostic value of long non-coding RNA H19 in glioma via integrated bioinformatics analyses

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