miR-181a Promotes Multiple Protumorigenic Functions by Targeting TGFβR3

Chitsazzadeh, Vida; Nguyen, Tran; Pulido, Álvaro de Mingo; Bittencourt, Bruna B.; Du, Lili; Adelmann, Charles H.; Rivera, Ivannie Ortiz; Nguyen, Khanh Thi-Thuy; Guerra, Leah; Davis, Andrew John; Napoli, Marco; Ma, Wencai; Davis, R. Eric; Rajapakshe, Kimal; Coarfa, Cristian; Flores, Elsa R.; Tsai, Kenneth Y.

doi:10.1016/j.jid.2021.09.040

Cited by 4 publications

(1 citation statement)

References 35 publications

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“…The current study showed that miR-181ab1 loss altered the expression levels of TGF-beta signature genes, suggesting miR-181 might also regulate the TGF-beta pathway. This notion has been confirmed in squamous cell carcinoma [ 69 ]. However, further investigations are needed to examine detailed aspects of molecular regulations between miR-181, the TGF-beta pathway, and EMT.…”

Section: Discussionmentioning

confidence: 71%

Liver-specific deletion of miR-181ab1 reduces liver tumour progression via upregulation of CBX7

Chen

Zhao

Zhang

et al. 2022

Cell. Mol. Life Sci.

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MiR-181 expression levels increased in hepatocellular carcinoma (HCC) compared to non-cancerous tissues. MiR-181 has been widely reported as a possible driver of tumourigenesis but also acts as a tumour suppressor. In addition, the miR-181 family regulates the development and function of immune and vascular cells, which play vital roles in the progression of tumours. More complicatedly, many genes have been identified as miR-181 targets to mediate the effects of miR-181. However, the role of miR-181 in the development of primary tumours remains largely unexplored. We aimed to examine the function of miR-181 and its vital mediators in the progression of diethylnitrosamine-induced primary liver cancers in mice. The size of liver tumours was significantly reduced by 90% in global (GKO) or liver-specific (LKO) 181ab1 knockout mice but not in hematopoietic and endothelial lineage-specific knockout mice, compared to WT mice. In addition, the number of tumours was significantly reduced by 50% in GKO mice. Whole-genome RNA-seq analysis and immunohistochemistry showed that epithelial-mesenchymal transition was partially reversed in GKO tumours compared to WT tumours. The expression of CBX7, a confirmed miR-181 target, was up-regulated in GKO compared to WT tumours. Stable CBX7 expression was achieved with an AAV/Transposase Hybrid-Vector System and up-regulated CBX7 expression inhibited liver tumour progression in WT mice. Hepatic CBX7 deletion restored the progression of LKO liver tumours. MiR-181a expression was the lowest and CBX7 expression the highest in iClust2 and 3 subclasses of human HCC compared to iClust1. Gene expression profiles of GKO tumours overlapped with low-proliferative peri-portal-type HCCs. Liver-specific loss of miR-181ab1 inhibited primary liver tumour progression via up-regulating CBX7 expression, but tumour induction requires both hepatic and non-hepatic miR-181. Also, miR-181ab1-deficient liver tumours may resemble low-proliferative periportal-type human HCC. Graphical abstract

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Section: Discussionmentioning

confidence: 71%

Liver-specific deletion of miR-181ab1 reduces liver tumour progression via upregulation of CBX7

Chen

Zhao

Zhang

et al. 2022

Cell. Mol. Life Sci.

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Asiaticoside-nitric oxide promoting diabetic wound healing through the miRNA-21-5p/TGF-β1/SMAD7/TIMP3 signaling pathway

Liu,

Zhao,

et al. 2024

Journal of Ethnopharmacology

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Functionally distinct cancer-associated fibroblast subpopulations establish a tumor promoting environment in squamous cell carcinoma

Schütz,

Solé-Boldo,

Lucena-Porcel

et al. 2023

Nat Commun

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Cutaneous squamous cell carcinoma (cSCC) is a serious public health problem due to its high incidence and metastatic potential. It may progress from actinic keratosis (AK), a precancerous lesion, or the in situ carcinoma, Bowen’s disease (BD). During this progression, malignant keratinocytes activate dermal fibroblasts into tumor promoting cancer-associated fibroblasts (CAFs), whose origin and emergence remain largely unknown. Here, we generate and analyze >115,000 single-cell transcriptomes from healthy skin, BD and cSCC of male donors. Our results reveal immunoregulatory and matrix-remodeling CAF subtypes that may derive from pro-inflammatory and mesenchymal fibroblasts, respectively. These CAF subtypes are largely absent in AK and interact with different cell types to establish a pro-tumorigenic microenvironment. These findings are cSCC-specific and could not be recapitulated in basal cell carcinomas. Our study provides important insights into the potential origin and functionalities of dermal CAFs that will be highly beneficial for the specific targeting of the cSCC microenvironment.

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miR-181a Promotes Multiple Protumorigenic Functions by Targeting TGFβR3

Cited by 4 publications

References 35 publications

Liver-specific deletion of miR-181ab1 reduces liver tumour progression via upregulation of CBX7

Liver-specific deletion of miR-181ab1 reduces liver tumour progression via upregulation of CBX7

Asiaticoside-nitric oxide promoting diabetic wound healing through the miRNA-21-5p/TGF-β1/SMAD7/TIMP3 signaling pathway

Functionally distinct cancer-associated fibroblast subpopulations establish a tumor promoting environment in squamous cell carcinoma

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