Low Expression of Long Noncoding RNA IRAIN Is Associated with Poor Prognosis in Non-M3 Acute Myeloid Leukemia Patients

Pashaiefar, Hossein; Izadifard, Marzieh; Yaghmaie, Marjan; Montazeri, Maryam; Gheisari, Elahe; Ahmadvand, Mohammad; Momeny, Majid; Ghaffari, Seyed H.; Kasaeian, Amir; Alimoghaddam, Kamran; Ghavamzadeh, Ardeshir

doi:10.1089/gtmb.2017.0281

Cited by 30 publications

(25 citation statements)

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“…The current results indicated that IRAIN expression was decreased in laryngeal carcinoma tissue, which is consistent with the findings of previous studies of AML (9,12), breast cancer (10) and renal cell carcinoma (30). However, the results are contrary to the findings of a study in NSCLC (11); this may be due to the fact that lncRNAs have tissue-specific expression patterns, which is different compared with the expression patterns of protein-coding genes (36,37).…”

Section: Discussionsupporting

confidence: 93%

“…Another previous study reported that IRAIN was significantly increased in non-small cell lung carcinoma (NSCLC) tissues, was related to tumor size and smoking status and that downregulation of IRAIN suppressed the proliferation of NSCLC cells via blocking cells in G 1 phase ( 11 ). Pashaiefar et al demonstrated, in 64 de novo non-M3 patients with AML compared with 51 healthy controls that poor prognosis with low IRAIN expression tended to have a higher white blood cell count and blast count, and had markedly shorter overall survival (OS) and relapse-free survival (RFS; P=0.044 and 0.009, respectively); in addition, the study found that patients with a refractory response to chemotherapy and those with subsequent relapse, had lower initial IRAIN expression and multivariate analysis identified IRAIN transcript expression as an independent prognostic factor for OS and RFS ( 12 ). Previous studies have reported that the IGF1R pathway is frequently dysregulated in laryngeal carcinoma ( 8 , 13 ); however, it has not been determined whether IRAIN serves a role in laryngeal carcinoma.…”

Section: Introductionmentioning

confidence: 95%

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Aberrant allelic‑switch of antisense lncRNA IRAIN may be an early diagnostic marker in laryngeal cancer

et al. 2020

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Laryngeal carcinoma is a common head and neck malignancy, however, the molecular mechanism of the disease has not yet been elucidated. The present study aimed to investigate the role of IGF1R antisense imprinted non-protein coding RNA (IRAIN) long non-coding (lnc) RNA in laryngeal carcinoma. In total, specimens of healthy pharynx tissue from 6 healthy individuals, carcinoma tissue and paracancerous tissue from 37 patients with laryngeal carcinoma were used in this study. The single nucleotide polymorphism (SNP) rs8034564 was used to distinguish the two parental alleles of IRAIN. DNA and RNA were extracted from tissue specimens and the IRAIN allelic gene was sequenced. Reverse transcription-quantitative PCR was used to determine the expression levels of IRAIN and Insulin-like growth factor 1 receptor (IGF1R) in laryngeal carcinoma and paracancerous tissue. Bisulfite genomic sequencing was used to determine IRAIN promoter DNA methylation status in laryngeal carcinoma tissue. The expression of IRAIN was di-allelic in healthy pharynx tissue, laryngeal carcinoma tissue and paracancerous tissue. Moreover, IRAIN expression in laryngeal carcinoma tissue was lower compared with paracancerous tissue (P<0.05). IRAIN expression was not associated with age, histological type, tumor stage and grade and lymph node metastasis. IRAIN allelic expression imbalance was present in laryngeal carcinoma and paracancerous tissue, but not in healthy pharynx tissue. SNP analysis (rs8034564) indicated there was an allelic-switch of the two parental alleles. Furthermore, epigenetic analysis revealed no extensive DNA methylation of CpG islands in the IRAIN gene promoter of laryngeal carcinoma. Therefore, it was suggested that IRAIN allele was non-imprinted in laryngeal carcinoma and healthy pharynx tissue. It was also demonstrated that IRAIN may be a potential tumor suppressor in laryngeal carcinoma, and that DNA methylation is not involved in the regulation of IRAIN gene immobilization in laryngeal carcinoma tissue. Thus, detection of IRAIN allelic expression imbalance and aberrant allele-switch may serve as an early diagnostic marker of laryngeal carcinoma.

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Section: Discussionsupporting

confidence: 93%

Section: Introductionmentioning

confidence: 95%

Aberrant allelic‑switch of antisense lncRNA IRAIN may be an early diagnostic marker in laryngeal cancer

et al. 2020

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“…Based on 64 de novo non-M3 AML patients, Pashaiefar et al found that low expression of IRAIN was independently associated with adverse prognosis: higher white blood cell count and blast counts and shorter OS and relapse-free survival. Besides, patients with refractory response to chemotherapies and those with subsequent relapse were more likely to show a lower initial IRAIN expression [183]. TUG1 has been in the spotlight of AML research.…”

Section: Prognostic Value Of Lncrnas In Acute Myeloid Leukemiamentioning

confidence: 99%

Role of microRNAs, circRNAs and long noncoding RNAs in acute myeloid leukemia

et al. 2019

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Acute myeloid leukemia (AML) is a malignant tumor of the immature myeloid hematopoietic cells in the bone marrow (BM). It is a highly heterogeneous disease, with rising morbidity and mortality in older patients. Although researches over the past decades have improved our understanding of AML, its pathogenesis has not yet been fully elucidated. Long noncoding RNAs (lncRNAs), microRNAs (miRNAs), and circular RNAs (circRNAs) are three noncoding RNA (ncRNA) molecules that regulate DNA transcription and translation. With the development of RNA-Seq technology, more and more ncRNAs that are closely related to AML leukemogenesis have been discovered. Numerous studies have found that these ncRNAs play an important role in leukemia cell proliferation, differentiation, and apoptosis. Some may potentially be used as prognostic biomarkers. In this systematic review, we briefly described the characteristics and molecular functions of three groups of ncRNAs, including lncRNAs, miRNAs, and circRNAs, and discussed their relationships with AML in detail.

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“…In this study, we show that lncRNA IRAIN was downregulated in RC cells and tissues, which was consistent with the results in RCC tissues and cells reported by Wang et al ( 25 ). Similarly, a study also showed downregulation of lncRNA IRAIN in non-M3 acute myeloid leukemia clinical specimens ( 26 ). Our data also demonstrated that lncRNA IRAIN downregulated VEGFA via recruitment of DNA methylation to the promoter region of VEGFA as evidenced by increased recruitment of Dnmt1, Dnmt3a, and Dnmt3b at the VEGFA promoter after overexpression of lncRNA IRAIN .…”

Section: Discussionmentioning

confidence: 87%

Long Non-coding RNA IRAIN Inhibits VEGFA Expression via Enhancing Its DNA Methylation Leading to Tumor Suppression in Renal Carcinoma

Yang

Luo

et al. 2020

Front. Oncol.

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Aims: Long non-coding RNA IRAIN (lncRNA IRAIN ) plays a critical role in numerous malignancies. However, the function of lncRNA IRAIN in renal carcinoma (RC) remains enigmatic. The purpose of this study is to characterize the effects of lncRNA IRAIN on RC progression. Methods: The expression pattern of lncRNA IRAIN and the vascular endothelial growth factor A (VEGFA) in RC tissues and cells was characterized by RT-qPCR and Western blot analysis. The roles of lncRNA IRAIN and VEGFA in the progression of RC were studied by gain- or loss-of-function experiments. Bioinformatics data analysis was used to predict CpG islands in the VEGFA promoter region. MSP was applied to detect the level of DNA methylation in RC cells. The interaction between lncRNA IRAIN and VEGFA was identified by RNA immunoprecipitation and RNA-protein pull down assays. Recruitment of DNA methyltransferases (Dnmt) to the VEGFA promoter region was achieved by chromatin immunoprecipitation. The subcellular localization of lncRNA IRAIN was detected by fractionation of nuclear and cytoplasmic RNA. Cell viability was investigated by CCK-8 assay, cell migration was tested by transwell migration assay, and apoptosis was analyzed by flow cytometry. The expression of epithelial–mesenchymal transition-related and apoptotic factors was evaluated by Western blot analysis. Finally, the effect of the lncRNA IRAIN /VEGFA axis was confirmed in an in vivo tumor xenograft model. Results: LncRNA IRAIN was poorly expressed in RC tissues and cells with a primary localization in the nucleus, while VEGFA was highly expressed. Overexpression of lncRNA IRAIN or knockdown of VEGFA inhibited cell proliferation and migration and induced the apoptosis of RC cells. Bioinformatics analysis indicated the presence of CpG islands in the VEGFA promoter region. Lack of methylation at specific sites in the VEGFA promoter region was detected through MSP assay. We found that lncRNA IRAIN was able to inhibit VEGFA expression through recruitment of Dnmt1, Dnmt3a, and Dnmt3b to the VEGFA promoter region. LncRNA IRAIN was also able to suppress RC tumor growth via repression of VEGFA in an in vivo mouse xenograft model. Conclusion: Our data shows that by downregulating VEGFA expression in RC, the lncRNA IRAIN has tumor-suppressive potential.

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Low Expression of Long Noncoding RNA IRAIN Is Associated with Poor Prognosis in Non-M3 Acute Myeloid Leukemia Patients

Abstract: Our finding suggests that IRAIN transcript levels may be a useful biomarker for the prognosis of non-M3 AML patients.

Cited by 30 publications

References 20 publications

Aberrant allelic‑switch of antisense lncRNA IRAIN may be an early diagnostic marker in laryngeal cancer

Aberrant allelic‑switch of antisense lncRNA IRAIN may be an early diagnostic marker in laryngeal cancer

Role of microRNAs, circRNAs and long noncoding RNAs in acute myeloid leukemia

Long Non-coding RNA IRAIN Inhibits VEGFA Expression via Enhancing Its DNA Methylation Leading to Tumor Suppression in Renal Carcinoma

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