Hypoxia-Inducible Factor-1α and its Role in the Proliferation of Retinoblastoma Cells

Fernandes, Bruno F.; Coates, James; Odashiro, Alexandre Nakao; Quezada, Carlos; Huynh, Aimee; Odashiro, Patricia R.; Odashiro, Maçanori; Burnier, Miguel N.

doi:10.1007/s12253-013-9728-8

Cited by 10 publications

(7 citation statements)

References 26 publications

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“…This is reasonable since HIF-1α is also detectable under normoxia in tumor tissues. 20,[36][37][38] In the following studies, the role of MIR17HG/miR-155-5p/HIF-1α in RB in hypoxic microenvironment should be further investigated.…”

Section: Discussionmentioning

confidence: 99%

LncRNA MIR17HG promotes the proliferation, migration, and invasion of retinoblastoma cells by up‐regulating HIF‐1α expression via sponging miR‐155‐5p

Jiang

Deng

Cai

et al. 2022

The Kaohsiung J of Med Scie

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Long non‐coding RNA (lncRNA) miR‐17‐92a‐1 cluster host gene (MIR17HG) is oncogenic in several cancers. This study was aimed to probe into its expression characteristics and biological functions in retinoblastoma (RB) and to explore its role in regulating microRNA‐155‐5p (miR‐155‐5p) and hypoxia‐inducible factor‐1α (HIF‐1α). In this study, paired RB samples were collected, and expression levels of MIR17HG, miR‐155‐5p, and HIF‐1α were examined by quantitative real‐time polymerase chain reaction (qRT‐PCR); the proliferation, migration, and invasion of RB cells were detected by cell counting kit‐8 (CCK‐8) and transwell assays; qRT‐PCR and Western blot were used to analyze the changes of miR‐155‐5p expression and HIF‐1α expression. We found that MIR17HG expression was significantly up‐regulated in RB samples, which was negatively correlated with miR‐155‐5p expression. The proliferation, migration, and invasion of RB cells were promoted by MIR17HG overexpression but inhibited by MIR17HG knockdown. MiR‐155‐5p suppressed the proliferation, migration, and invasion of RB cells. MIR17HG positively regulated the expression of HIF‐1α on both mRNA and protein levels in RB cells. Additionally, miR‐155‐5p was identified as a target of MIR17HG. The data in this study suggest that MIR17HG exerts oncogenic effects in RB via the miR‐155‐5p/HIF‐1α axis.

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Section: Discussionmentioning

confidence: 99%

LncRNA MIR17HG promotes the proliferation, migration, and invasion of retinoblastoma cells by up‐regulating HIF‐1α expression via sponging miR‐155‐5p

Jiang

Deng

Cai

et al. 2022

The Kaohsiung J of Med Scie

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“…HIF-1α is an oxygen-dependent subunit of HIF-1, which has another constitutively expressed (HIF-1β subunit); HIF-1α and HIF-1β are members of the basic helix-loop-helix-Per-ARNT-Sim (bHLH-PAS) protein family (17). In previous studies, deregulated HIF-1α was observed in RB hypoxic regions (18), and HIF-1α levels were associated with the survival and proliferation of RB cells (19). Therefore, we hypothesized that miR-320 may affect RB development by influencing HIF-1α levels.…”

Section: Introductionmentioning

confidence: 99%

MicroRNA-320 regulates autophagy in retinoblastoma by targeting hypoxia inducible factor-1α

Liang¹,

Chen²,

Zhu³

2017

Experimental and Therapeutic Medicine

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Abstract. Retinoblastoma (RB) is the most common malignancy in children. Due to refractory mechanisms of chemoresistance and the toxicity of chemotherapies, novel therapies for RB treatment are urgently required. MicroRNA-320 (miR-320) is believed to be associated with the tumorigenesis of RB, although the mechanism remains unclear. Considering the hypoxic intratumoral region, the roles of miR-320 and hypoxia inducible factor-1α (HIF-1α) in the regulation of autophagy were investigated in 30 human RB samples and WERI-RB1 cells. The results demonstrated that HIF-1α was the downstream target of miR-320, and decreased miRNA-320 or HIF-1α lead to the inhibition of autophagy in WERI-RB1 cells. Compared with WERI-RB1 cells that were not transfected, silenced HIF-1α caused a 1.41-fold increase (P<0.01) in p62, a 2.71-fold decrease of Beclin1, and inhibited miRNA-320. Silenced HIF-1α also resulted in 7.29-and 7.43-fold increases in phosphorylated-mechanistic target of rapamycin (mTOR) and mTOR, respectively. In conclusion, the present results suggest that miRNA-320 may regulate the development of autophagy by targeting HIF-1α and autophagy-related proteins in RB under hypoxic conditions.

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“…In conclusion, Rb tumors undergo ongoing hypoxic adaptation to allow continued proliferation and invasion in an increasingly oxygen-depleted environment ( 47, 48 ), and our findings implicate ESRRG and its decoupling from normal homeostatic regulation by RB1 and BCOR as a key mediator of this hypoxic adaptation. Further studies are warranted to investigate the potential role for inhibiting ESRRG in the management of Rb.…”

Section: Discussionmentioning

confidence: 62%

RB1 loss triggers dependence on ESRRG in retinoblastoma

Field

Kuznetsoff

Zhang

et al. 2021

Preprint

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Retinoblastoma (Rb) is a deadly childhood eye cancer that is classically initiated by inactivation of the RB1 tumor suppressor. Clinical management continues to rely on nonspecific chemotherapeutic agents that are associated with treatment resistance and toxicity. Here, we analyzed 103 whole exomes, 16 whole transcriptomes, 5 single-cell transcriptomes, and 4 whole genomes from primary Rb tumors to identify novel Rb dependencies. Several recurrent genomic aberrations implicate estrogen-related receptor gamma (ESRRG) in Rb pathogenesis. RB1 directly interacts with and inhibits ESRRG, and RB1 loss uncouples ESRRG from negative regulation. ESRRG regulates genes involved in retinogenesis and oxygen metabolism in Rb cells. ESRRG is preferentially expressed in hypoxic Rb cells in vivo. Depletion or inhibition of ESRRG causes marked Rb cell death which is exacerbated in hypoxia. These findings reveal a novel dependency of Rb cells on ESRRG, and they implicate ESRRG as a potential therapeutic vulnerability in Rb.

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Hypoxia-Inducible Factor-1α and its Role in the Proliferation of Retinoblastoma Cells

Cited by 10 publications

References 26 publications

LncRNA MIR17HG promotes the proliferation, migration, and invasion of retinoblastoma cells by up‐regulating HIF‐1α expression via sponging miR‐155‐5p

LncRNA MIR17HG promotes the proliferation, migration, and invasion of retinoblastoma cells by up‐regulating HIF‐1α expression via sponging miR‐155‐5p

MicroRNA-320 regulates autophagy in retinoblastoma by targeting hypoxia inducible factor-1α

RB1 loss triggers dependence on ESRRG in retinoblastoma

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