The lncRNA CASC15 regulates SOX4 expression in RUNX1-rearranged acute leukemia

Fernando, Thilini R.; Contreras, Jorge R.; Zampini, Matteo; Rodríguez-Malavé, Norma I.; Alberti, Michael O.; Anguiano, Jaime; Tran, Tiffany; Palanichamy, Jayanth Kumar; Gajeton, Jasmine; Ung, Nolan; Aros, Cody J.; Waters, Ella V.; Casero, David; Basso, Giuseppe; Pigazzi, Martina; Rao, Dinesh S.

doi:10.1186/s12943-017-0692-x

Cited by 125 publications

(101 citation statements)

References 61 publications

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“…High expression of CASC15 led to myeloidpredominant BM development, decreased engraftment, and colony formation. Researchers also found that CASC15 positively regulated YY1-mediated SOX4 promoter [178].…”

Section: Runx1 Mutation-related Lncrnasmentioning

confidence: 98%

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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Section: Runx1 Mutation-related Lncrnasmentioning

confidence: 98%

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

et al. 2019

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“…Here we report that a lncRNA, named CASC15, is transcriptionally activated by the hypoxia/HIF-1α signaling and promotes SOX4 expression in a cis-acting manner in NSCLC. CASC15 was firstly identified as a pivotal tumor suppressor in neuroblastoma but was later reported to play an oncogenic role in many other cancer types, such as melanoma, gastric cancer, liver cancer, and acute leukemia [21,22,[27][28][29]. Nevertheless, these studies did not uncover the signaling pathways that might activate the expression of CASC15.…”

Section: Discussionmentioning

confidence: 99%

“…Numerous studies have demonstrated that CASC15 expression is elevated in a variety of human malignancies, such as melanoma, gastric cancer, liver cancer, and acute leukemia [22,[27][28][29]. However, to date, little is known about the mechanisms governing CASC15 upregulation in cancer.…”

Section: Casc15 Is Transcriptionally Activated By the Hypoxia/hif-1α mentioning

confidence: 99%

Hypoxia-sensitive Long Noncoding RNA CASC15 Promotes Lung Tumorigenesis by Regulating the SOX4/β-catenin Axis

Sun

Xiong

Jiang

et al. 2020

Preprint

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Background: Accumulating evidence has demonstrated that long non-coding RNAs (lncRNAs) are involved in the hypoxia-related cancer process and play pivotal roles in enabling malignant cells to survive under hypoxic stress. However, the molecular crosstalk between lncRNAs and hypoxia signaling cascades in non-small cell lung cancer (NSCLC) remains largely elusive. Methods: Firstly, we identified differentially expressed lncRNA cancer susceptibility candidate 15 (CASC15) as associated with NSCLC based on bioinformatic data. The clinical significance of CASC15 in lung cancer was investigated by Kaplan-Meier survival analysis. Then, we modulated CASC15 expression in NSCLC cell lines by RNAi. CCK-8 and transwell assays were carried out to examine the effects of CASC15 on proliferation and migration of NSCLC cells. Upstream activator and downstream targets of CASC15 were validated by luciferase reporter assay, qRT-PCR, Western blotting, and chromatin immunoprecipitation (ChIP). Lastly, RNA in situ hybridization (RNA-ISH) and immunohistochemistry (IHC) were performed to confirm the genetic relationships between CASC15 and related genes in clinical samples. Results: CASC15 was highly expressed in NSCLC tissues and closely associated with poor prognosis. Loss-of-function analysis demonstrated that CASC15 was essential for NSCLC cell migration and growth. Mechanistic study revealed that CASC15 was transcriptionally activated by hypoxia signaling in NSCLC cells. Further analysis showed that hypoxia-induced CASC15 transactivation was mainly dependent on hypoxia-inducible factor 1α (HIF-1α) and hypoxia response elements (HREs) located in CASC15 promoter. CASC15 promotes the expression of its chromosomally nearby gene, SOX4. Then SOX4 functions to stabilize β-catenin protein, thereby enhancing the proliferation and migration of NSCLC cells. HIF-1α/CASC15/SOX4/β-catenin pathway was activated in a substantial subset of NSCLC patients. Conclusions: HIF-1α/CASC15/SOX4/β-catenin axis plays an essential role in the development and progression of NSCLC. The present work provides new evidence that lncRNA CASC15 holds great promise to be used as novel biomarkers for NSCLC. Blocking the HIF-1α/CASC15/SOX4/β-catenin axis can serve as a potential therapeutic strategy for treating NSCLC.

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“…With the continuous improvement and progress of experimental technology, more and more new lncRNAs have been discovered by RNA sequencing technology, which play a main role in the occurrence and development of diseases and malignant progress [2,25,37]. Many studies have shown that many lncRNAs express differently in AML and can regulate their functions [11,12,21,30]. However, the function and molecular mechanism of many lncRNAs associated with AML are still unclear.…”

Section: Discussionmentioning

confidence: 99%

Long Noncoding RNA HOXA-AS2 Functions as an Oncogene by Binding to EZH2 and Suppressing LATS2 in AML

Feng

et al. 2020

Preprint

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BackgroundLong noncoding RNAs (lncRNAs) plays an important role in the development of physiology and pathology. Many reports have shown that LncRNA HOXA cluster antisense RNA 2 (HOXA-AS2) is a carcinogen and plays an important role in many tumors, but there are few reports on its role in Acute myeloid leukemia (AML). MethodsThe expression of HOXA-AS2 in AML cell line was detected by qRT-PCR. AML cases from the public database (GEPIA) were also included in this study. Cell counting kit-8 (CCK-8) assay, flow cytometry, immunofluorescence and Western blot were used to detect the role of HOXA-AS2 in AML cells. Luciferase reporter gene detection, RIP, RNA pull-down and RNA-ChIP detection were used to demonstrate the molecular biological mechanism of HOXA-AS2 in AML.ResultsOur results show that HOXA-AS2 was upregulated in AML cell lines and tissues, and the overexpression of HOXA-AS2 is negatively correlated with the survival of patients. Silencing HOXA-AS2 can inhibit the proliferation and induce differentiation of AML cells in vitro and in vivo. After overexpressing HOXA-AS2, it will show the opposite result. Moreover, more in-depth mechanism studies show that HOXA-AS2 exerts its carcinogenicity mainly by binding with the epigenetic inhibitor Enhancer of zeste homolog 2 (EZH2) and then inhibiting the expression of Large Tumor Suppressor 2 (LATS2). ConclusionsTaken together, our results highlight the important role of HOXA-AS2 in AML, suggesting that HOXA-AS2 may be an effective therapeutic target for patients with AML.

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The lncRNA CASC15 regulates SOX4 expression in RUNX1-rearranged acute leukemia

Cited by 125 publications

References 61 publications

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

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

Hypoxia-sensitive Long Noncoding RNA CASC15 Promotes Lung Tumorigenesis by Regulating the SOX4/β-catenin Axis

Long Noncoding RNA HOXA-AS2 Functions as an Oncogene by Binding to EZH2 and Suppressing LATS2 in AML

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