RhoBTB Proteins Regulate the Hippo Pathway by Antagonizing Ubiquitination of LKB1

Nguyen, Thanh Hung; Ralbovska, Adela; Kugler, Jan-Michael

doi:10.1534/g3.120.401038

Cited by 8 publications

(5 citation statements)

References 46 publications

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“…RhoBTB1 is a tumor suppressor gene involved in different types of cancer [7,90], but its role in cardiac pathologies is still unclear. Interestingly, a recent study also suggested a regulatory role of RhoBTB on the Hippo signaling [98]. This role was reported in Drosophila and human (HEK293T) cells and was shown to be mediated by ubiquitination-dependent regulation of LKB1 kinase [151].…”

Section: Micrornas As Targets For Cardiomyocyte Proliferationmentioning

confidence: 78%

Non-coding RNAs: emerging players in cardiomyocyte proliferation and cardiac regeneration

2020

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Soon after birth, the regenerative capacity of the mammalian heart is lost, cardiomyocytes withdraw from the cell cycle and demonstrate a minimal proliferation rate. Despite improved treatment and reperfusion strategies, the uncompensated cardiomyocyte loss during injury and disease results in cardiac remodeling and subsequent heart failure. The promising field of regenerative medicine aims to restore both the structure and function of damaged tissue through modulation of cellular processes and regulatory mechanisms involved in cardiac cell cycle arrest to boost cardiomyocyte proliferation. Non-coding RNAs (ncRNAs), such as microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs) are functional RNA molecules with no protein-coding function that have been reported to engage in cardiac regeneration and repair. In this review, we summarize the current understanding of both the biological functions and molecular mechanisms of ncRNAs involved in cardiomyocyte proliferation. Furthermore, we discuss their impact on the structure and contractile function of the heart in health and disease and their application for therapeutic interventions.

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Section: Micrornas As Targets For Cardiomyocyte Proliferationmentioning

confidence: 78%

Non-coding RNAs: emerging players in cardiomyocyte proliferation and cardiac regeneration

2020

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“…Genes encoding RhoBTB proteins exhibit ubiquitous but tissue-differential expression ( Berthold et al, 2008b ; Ji and Rivero, 2016 ; Nguyen et al, 2020 ). RhoBTB1 and RhoBTB2 have been regarded as tumor suppressors.…”

Section: Discussionmentioning

confidence: 99%

“…RhoBTB1 and RhoBTB2 are highly similar, whereas RhoBTB3 is the most divergent member ( Aspenström et al, 2004 ; 2007 ; Berthold et al, 2008b ; Espinosa et al, 2009 ). Interestingly, the RhoGTPase domain of RhoBTB3 binds and hydrolyses ATP, whereas that of RhoBTB1/2 binds GTP ( Aspenström et al, 2004 ; 2007 ; Berthold et al, 2008a ; Nguyen et al, 2020 ). Moreover, only RhoBTB3 bears an isoprenylation CAAX motif that is typical of classical RhoGTPases in the C-terminal region ( Ji and Rivero, 2016 ; Junaid et al, 2014 ; Manolaridis et al, 2013 ).…”

Section: Discussionmentioning

confidence: 99%

RhoBTB3 Regulates Proliferation and Invasion of Breast Cancer Cells via Col1a1

Kim

2022

Molecules and Cells

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Breast cancer is the leading cause of cancer-related death in women worldwide, despite medical and technological advancements. The RhoBTB family consists of three isoforms: RhoBTB1, RhoBTB2, and RhoBTB3. RhoBTB1 and RhoBTB2 have been proposed as tumor suppressors in breast cancer. However, the roles of RhoBTB3 proteins are unknown in breast cancer. Bioinformatics analysis, including Oncomine, cBioportal, was used to evaluate the potential functions and prognostic values of RhoBTB3 and Col1a1 in breast cancer. qRT-PCR analysis and immunoblotting assay were performed to investigate relevant expression. Functional experiments including proliferation assay, invasion assay, and flow cytometry assay were conducted to determine the role of RhoBTB3 and Col1a1 in breast cancer cells. RhoBTB3 mRNA levels were significantly up-regulated in breast cancer tissues as compared to in adjacent normal tissues. Moreover, RhoBTB3 expression was found to be associated with Col1a1 expression. Decreasing RhoBTB3 expression may lead to decreases in the proliferative and invasive properties of breast cancer cells. Further, Col1a1 knockdown in breast cancer cells limited the proliferative and invasive ability of cancer cells. Knockdown of RhoBTB3 may exert inhibit the proliferation, migration, and metastasis of breast cancer cells by repressing the expression of Col1a1, providing a novel therapeutic strategy for treating breast cancer.

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“…Two SMGs from our analysis (LATS1 and NF2) are core members of the HIPPO signalling pathway, while SMGs FAT1, JUB and STK11 are known regulators of HIPPO signalling [21][22][23] . Mutations in LATS1, FAT1, JUB, STK11 or NF2 (the latter two of which are signi cantly mutated speci cally in C2 tumours, Fig.…”

Section: C2 Tumours Display Hippo Pathway Alterations and Increased Yap1 Activitymentioning

confidence: 99%

Integrated analysis of cervical squamous cell carcinoma cohorts from three continents reveals conserved subtypes of prognostic significance.

Chakravarthy

Reddin

Henderson

et al. 2021

Preprint

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Human papillomavirus (HPV)-associated cervical cancer represents one of the leading causes of cancer death worldwide. Although low-middle income countries are disproportionately affected, our knowledge of the disease predominantly originates from populations in high-income countries. Using the largest multi-omic analysis of cervical squamous cell carcinoma (CSCC) to date, totalling 643 tumours and representing patient populations from the USA, Europe and Sub-Saharan Africa, we identify two CSCC subtypes (C1 and C2) with differing prognosis. C1 tumours are largely HPV16-driven, display increased cytotoxic T-lymphocyte infiltration and frequently harbour PIK3CA and EP300 mutations. C2 tumours are associated with shorter overall survival, are frequently driven by HPVs from the HPV18-containing alpha-7 clade, harbour alterations in the Hippo signalling pathway and increased expression of immune checkpoint genes, B7-H3 (also known as CD276) and NT5E (also known as CD73) and PD-L2 (also known as PDCD1LG2). In conclusion, we identify two novel, therapy-relevant CSCC subtypes that share the same defining characteristics across three geographically diverse cohorts.

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RhoBTB Proteins Regulate the Hippo Pathway by Antagonizing Ubiquitination of LKB1

Cited by 8 publications

References 46 publications

Non-coding RNAs: emerging players in cardiomyocyte proliferation and cardiac regeneration

Non-coding RNAs: emerging players in cardiomyocyte proliferation and cardiac regeneration

RhoBTB3 Regulates Proliferation and Invasion of Breast Cancer Cells via Col1a1

Integrated analysis of cervical squamous cell carcinoma cohorts from three continents reveals conserved subtypes of prognostic significance.

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