Hypoxia-induced lncRNA RBM5-AS1 promotes tumorigenesis via activating Wnt/β-catenin signaling in breast cancer

Li, Xinping; Yang, Jingyan; Ni, Ruiqi; Chen, Jintian; Zhou, Yiding; Song, Hao; Jin, Liang; Pan, Yi

doi:10.1038/s41419-022-04536-y

Cited by 19 publications

(9 citation statements)

References 23 publications

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“…More recently, Li and colleagues have also demonstrated the involvement of hypoxia-induced long non-coding RNA RBM5-AS1 in mediating proliferation, migration, invasion, EMT, and stemness maintenance in breast cancer cells under the control of RUNX family transcription factor 2 (RUNX2). Specifically, the authors demonstrated that enrichment of RBM5-AS1 enhanced Wnt signaling by repressing β-catenin degradation and reinforcing the β-catenin:TCF7L2 transcriptional complex ( Li et al, 2022 ).…”

Section: Wnt Signaling and Breast Cscsmentioning

confidence: 99%

Wnt Signaling in the Breast: From Development to Disease

Oliveira

Laithy

Bruna³

et al. 2022

Front. Cell Dev. Biol.

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The Wnt cascade is a primordial developmental signaling pathway that plays a myriad of essential functions throughout development and adult homeostasis in virtually all animal species. Aberrant Wnt activity is implicated in embryonic and tissue morphogenesis defects, and several diseases, most notably cancer. The role of Wnt signaling in mammary gland development and breast cancer initiation, maintenance, and progression is far from being completely understood and is rather shrouded in controversy. In this review, we dissect the fundamental role of Wnt signaling in mammary gland development and adult homeostasis and explore how defects in its tightly regulated and intricated molecular network are interlinked with cancer, with a focus on the breast.

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Section: Wnt Signaling and Breast Cscsmentioning

confidence: 99%

Wnt Signaling in the Breast: From Development to Disease

Oliveira

Laithy

Bruna³

et al. 2022

Front. Cell Dev. Biol.

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“…Our previous studies revealed that downregulated RBM5 promotes the progression of BC by activating the Wnt/β-catenin signaling pathway [9]. Consistent with these findings, RBM5 has been shown to promote apoptosis through the inhibition of Wnt/β-catenin signaling [6,10]. However, the specific mechanism of action has not been fully elucidated.…”

Section: Introductionmentioning

confidence: 80%

Downregulated RBM5 Enhances CARM1 Expression and Activates the PRKACA/GSK3β Signaling Pathway through Alternative Splicing-Coupled Nonsense-Mediated Decay

Zhang,

Li,

Han

et al. 2023

Cancers

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Downregulated RNA-binding motif protein 5 (RBM5) promotes the development and progression of various tumors, including bladder cancer (BC). Alternative splicing (AS) plays a crucial role in the progression of cancer by producing protein isomers with different functions or by promoting nonsense-mediated mRNA decay (NMD). However, whether RBM5 modulates the progression of BC through AS-NMD remains unexplored. In this study, we revealed that the downregulation of RBM5 expression promoted the expression of coactivator-associated arginine methyltransferase 1 (CARM1) in BC cells and tissues. Increased expression of CARM1 facilitated the activation of the Wnt/β-catenin axis and cell proliferation, which then contributed to the poor prognosis of patients with BC. Interestingly, RBM5 bound directly to CARM1 mRNA and participated in AS-NMD, downregulating the expression of CARM1. In addition, we revealed that protein kinase catalytic subunit alpha (PRKACA) functioned as a phosphorylated kinase of GSK3β, was regulated by CARM1 at the transcription level, and promoted the growth and progression of BC cells. Furthermore, in this study, we demonstrated a regulatory mechanism of Wnt/β-catenin activation through the RBM5/CARM1/PRKACA axis and identified a novel potential target for treating BC.

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“…Hypoxia induces the transcriptional upregulation of lncRNA six-transmembrane epithelial antigen of the prostate 3 (STEAP3)-AS1 expression in colorectal cancer by HIF-1α, which subsequently enhances STEAP3 expression through competitive interaction with YTH N6-methyladenosine RNA binding protein F2 31 . Li et al discovered that RNA binding motif protein 5-AS1 hastened the Wnt/β-catenin signalling pathway through the upregulation of β-catenin to promote the breast cancer process under hypoxic conditions 32 .…”

Section: Discussionmentioning

confidence: 99%

“…Studies have shown that lncRNAs are variably expressed in hypoxic environments 22,31,32 . Our previous research con rmed that hypoxia induces an increase in lncRNA-ZEB1-AS1 and lncRNA-NUTF2P3-001 16,17 ; hence, we next sought to demonstrate whether the variational expression of MANCR was signi cant in hypoxia induction.…”

Section: Hypoxia Induced Overexpression Of Lncrna-mancr Expression In...mentioning

confidence: 99%

The role of LncRNA-MANCR induced by HIF-1a drive the malignant progression of pancreatic cancer by targeting miRNA-494/SIRT1 signaling axis under hypoxic conditions

Jin,

Hu,

Tian

et al. 2024

Preprint

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Purpose Accumulating evidence has focused on the vital roles of long non-coding RNAs (lncRNAs) in the hypoxic extracellular microenvironment of multiple human tumours. This study revealed the prospective biological role and fundamental mechanisms of hypoxia-induced lncRNA-MANCR (MANCR), which is notably upregulated in pancreatic cancer (PC). This work uncovered the potential biological function and underlying mechanisms of hypoxia-induced MANCR, which is significantly elevated in PC. Methods Microarray assays confirmed MANCR expression in the tissues of patients with PC and patients with chronic pancreatitis (CP), which positively correlated with sirtuin-1 (SIRT1) mRNA levels. In PC cells, lncRNA expression levels were compared using RNA sequencing. The impact of MANCR on tumour proliferation and metastasis of PC cells and in vivo models cultured under either normoxic or hypoxic conditions was evaluated using gain- and loss-of-function experiments. Chromatin immunoprecipitation and luciferase assays were employed to gauge binding within the hypoxia-inducible factor-1α (HIF-1α)/MANCR/miRNA-494/SIRT1 pathway. Additionally, the association between MANCR expression and the clinical outcomes of patients with PC was confirmed. Results MANCR is significantly upregulated in PC cells under hypoxic conditions, which is closely linked to poor prognosis in patients with PC. Depletion of MANCR repressed in vitro proliferation, migration, and invasion of PC cells and in vivo growth of PC xenograft tumours. We further demonstrated that MANCR is localised in the cytoplasm and competitively binds miR-494, which directly targets SIRT1. Mechanically, overexpression of SIRT1 improved the stability of the HIF-1α protein through deacetylation, leading to enhanced HIF-1α assembly. Moreover, MANCR underwent transcriptional regulation by HIF-1α in a hypoxic setting. This modulation was ascribed to HIF-1α binding to hypoxia response elements present in the MANCR promoter sequence. Furthermore, increased MANCR expression corresponded with lymphatic and distant metastases in patients with PC. Conclusions All data revealed the potential possibility of feedback between MANCR and HIF-1α, which may be conducive to hypoxia-induced oncogenicity and PC tumorigenesis, thereby providing a suitable therapeutic target.

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Hypoxia-induced lncRNA RBM5-AS1 promotes tumorigenesis via activating Wnt/β-catenin signaling in breast cancer

Cited by 19 publications

References 23 publications

Wnt Signaling in the Breast: From Development to Disease

Wnt Signaling in the Breast: From Development to Disease

Downregulated RBM5 Enhances CARM1 Expression and Activates the PRKACA/GSK3β Signaling Pathway through Alternative Splicing-Coupled Nonsense-Mediated Decay

The role of LncRNA-MANCR induced by HIF-1a drive the malignant progression of pancreatic cancer by targeting miRNA-494/SIRT1 signaling axis under hypoxic conditions

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