Long non-coding antisense RNA HYOU1-AS is essential to human breast cancer development through competitive binding hnRNPA1 to promote HYOU1 expression

Hao, Aixin; Wang, Yu; Zhang, Xiao; Li, Jialiang; Li, Yingzhou; Li, Dangdang; Kulik, George; Sui, Guangchao

doi:10.1016/j.bbamcr.2021.118951

Cited by 13 publications

(8 citation statements)

References 68 publications

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“…Recent studies have also implicated GRP170 in tumorigenesis associated with several cancers, including bladder, papillary thyroid, and breast. Of note, overexpression of GRP170 correlates with poor outcomes, increased cell mobility, and proliferation (Wang et al, 2023), (Wang et al, 2021), (Lee et al, 2021), (Hao et al, 2021). In addition, a requirement for GRP170 NEF activity in both cholera toxin and polyomavirus pathogenesis was uncovered, since GRP170 releases BiP from the toxin/virus, which is needed for ER to the cytosol retrotranlsocation and pathogenesis (Inoue and Tsai, 2015), (Williams et al, 2015).…”

Section: Discussionmentioning

confidence: 99%

Loss of Grp170 results in catastrophic disruption of endoplasmic reticulum functions

Mann,

Melendez-Suchi,

Sukhoplyasova

et al. 2023

Preprint

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GRP170, a product of the Hyou1 gene, is required for mouse embryonic development, and its ablation in kidney nephrons leads to renal failure. Unlike most chaperones, GRP170 is the lone member of its chaperone family in the ER lumen. However, the cellular requirement for GRP170, which both binds non-native proteins and acts as nucleotide exchange factor for BiP, is poorly understood. Here, we report on the isolation of embryonic fibroblasts from mice in which LoxP sites were engineered in the Hyou1 loci (Hyou1LoxP/LoxP). A doxycycline-regulated Cre recombinase was also stably introduced into these cells. Induction of Cre resulted in excision of Hyou1 and depletion of Grp170 protein, culminating in apoptotic cell death. As Grp170 levels fell we observed increased steady-state binding of BiP to a client, slowed degradation of a misfolded BiP substrate, and BiP accumulation in NP40-insoluble fractions. Consistent with disrupted BiP functions, we observed reactivation of BiP storage pools and induction of the unfolded protein response (UPR) in futile attempts to provide compensatory increases in ER chaperones and folding enzymes. Together, these results provide insights into the cellular consequences of controlled Grp170 loss and insights into mutations in the Hyou1 locus and human disease.

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Section: Discussionmentioning

confidence: 99%

Loss of Grp170 results in catastrophic disruption of endoplasmic reticulum functions

Mann,

Melendez-Suchi,

Sukhoplyasova

et al. 2023

Preprint

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“… 14 , 15 For example, serine and arginine rich splicing factor 1 (SRSF1) has been shown to play an important role in BRCA by regulating alternative splicing, 16 and heterogeneous nuclear ribonucleoprotein A1 (HNRNPA1) affected the progression of triple-negative breast cancer by regulating hypoxia up-regulated 1 (HYOU1) mRNA expression. 17 In addition, N-acetyltransferase 10 (NAT10) regulates cell cycle checkpoint control and resistance to DNA-damaging chemotherapy and radiotherapy by affecting MORC family CW-type zinc finger 2 (MORC2) acetylation in BRCA. 18 Furthermore, interleukin enhancer binding factor 3 (ILF3) promoted breast tumorigenicity by regulating sustained urokinase-type plasminogen activator (uPA) expression, 19 and DEAD-box helicase 17 (DDX17) enhanced the tumorigenic and stem-like features of SRY-box 2 (SOX2) by promoting its binding to its target genes in ER-positive BRCA.…”

Section: Discussionmentioning

confidence: 99%

Development and validation of novel prognostic models based on RNA-binding proteins in breast cancer

et al. 2022

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Objectives We aimed to construct novel prognostic models based on RNA-binding proteins (RBPs) in breast cancer (BRCA) and explore their roles in this disease and their effects on tumor-infiltrating immune cells (TIICs). Methods Datasets were downloaded from the Gene Expression Omnibus (GEO) database. Functions and prognostic values of RBPs were systematically investigated using a series of bioinformatics analysis methods. TIICs were assessed using CIBERSORT. Results Overall, 138 differentially expressed RBPs were identified, of which 86 were upregulated and 52 were downregulated. Of these, 13 RBPs were identified as prognosis-related and adopted to construct an overall survival (OS) model, while 12 RBPs were used for the relapse-free survival (RFS) model. High-risk patients had poorer OS and RFS rates than low-risk patients. The results indicate that the OS and RFS models are good prognostic models with reliable predictive abilities. In addition, the proportions of CD8, CD4 naïve, and CD4 memory resting T cells, as well as resting dendritic cells, were significantly different between the low-risk and high-risk groups in the OS model. Conclusions OS and RFS signatures can be used as reliable BRCA prognostic biomarkers. This work will help understand the prognostic roles and functions of RBPs in BRCA.

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“…The Hpoxia up-regulated 1 (HYOU1) gene is associated with poor clinical outcomes in breast cancer patients. Interestingly, the same gene locus expresses a lncRNA from the opposite strand named HYOU1-AS1, which aids in HYOU1 mediated TNBC cell proliferation and progression through competitively binding to heterogeneous nuclear ribonucleoprotein A1 (hnRNPA1), an RNA binding protein that may post-transcriptionally inhibit HYOU1 mRNA ( 69 ). HIF1α transcriptionally activates the lncRNA N-Myc downstream regulated 1-overlapping 1 (NDRG1-OT1) in breast cancer cells, which aids in cancer progression by destabilizing its parent gene NDRG1 both at transcriptional and post-translational levels.…”

Section: Hypoxia-driven Ncrnas In Breast Cancermentioning

confidence: 99%

Hypoxia-driven ncRNAs in breast cancer

H. Al-Zuaini,

Rafiq Zahid,

Xiao

et al. 2023

Front. Oncol.

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Low oxygen tension, or hypoxia is the driving force behind tumor aggressiveness, leading to therapy resistance, metastasis, and stemness in solid cancers including breast cancer, which now stands as the leading cause of cancer-related mortality in women. With the great advancements in exploring the regulatory roles of the non-coding genome in recent years, the wide spectrum of hypoxia-responsive genome is not limited to just protein-coding genes but also includes multiple types of non-coding RNAs, such as micro RNAs, long non-coding RNAs, and circular RNAs. Over the years, these hypoxia-responsive non-coding molecules have been greatly implicated in breast cancer. Hypoxia drives the expression of these non-coding RNAs as upstream modulators and downstream effectors of hypoxia inducible factor signaling in the favor of breast cancer through a myriad of molecular mechanisms. These non-coding RNAs then contribute in orchestrating aggressive hypoxic tumor environment and regulate cancer associated cellular processes such as proliferation, evasion of apoptotic death, extracellular matrix remodeling, angiogenesis, migration, invasion, epithelial-to-mesenchymal transition, metastasis, therapy resistance, stemness, and evasion of the immune system in breast cancer. In addition, the interplay between hypoxia-driven non-coding RNAs as well as feedback and feedforward loops between these ncRNAs and HIFs further contribute to breast cancer progression. Although the current clinical implications of hypoxia-driven non-coding RNAs are limited to prognostics and diagnostics in breast cancer, extensive explorations have established some of these hypoxia-driven non-coding RNAs as promising targets to treat aggressive breast cancers, and future scientific endeavors hold great promise in targeting hypoxia-driven ncRNAs at clinics to treat breast cancer and limit global cancer burden.

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Long non-coding antisense RNA HYOU1-AS is essential to human breast cancer development through competitive binding hnRNPA1 to promote HYOU1 expression

Cited by 13 publications

References 68 publications

Loss of Grp170 results in catastrophic disruption of endoplasmic reticulum functions

Loss of Grp170 results in catastrophic disruption of endoplasmic reticulum functions

Development and validation of novel prognostic models based on RNA-binding proteins in breast cancer

Hypoxia-driven ncRNAs in breast cancer

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