HDAC inhibitors promote pancreatic stellate cell apoptosis and relieve pancreatic fibrosis by upregulating miR-15/16 in chronic pancreatitis

Ji, Ting; Feng, Weiguang; Xiangcheng, Zhang; Zang, Kui; Zhu, Xingxing; Shang, Futai

doi:10.1007/s13577-020-00387-x

Cited by 19 publications

(11 citation statements)

References 42 publications

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“…Smad7 is an inhibitory protein of the TGF-β/Smad signaling pathway that can effectively inhibit the phosphorylation of signal activators (Smad2 and Smad3) and subsequent downstream signal activation [20]. However, other studies have shown that miR-16 can significantly inhibit the expression of smad2 [21], smad3 [22], and smad5 [23] in fibroblasts, as well as the phenotypic remodeling process of fibroblasts to myofibroblasts induced by TGF-β in many ways, thus playing an anti-fibrotic role.…”

Section: Regulation Of Cell Transformationmentioning

confidence: 99%

The Molecular Mechanisms and Function of miR-15a/16 Dysregulation in Fibrotic Diseases

Wen

Zhang

Zhou

et al. 2022

IJMS

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MicroRNAs (miRNAs) are a class of short, endogenous, non-coding, single-stranded RNAs that can negatively regulate the post-transcriptional expression of target genes. Among them, miR-15a/16 is involved in the regulation of the occurrence and development of fibrosis in the liver, lungs, heart, kidneys, and other organs, as well as systemic fibrotic diseases, affecting important cellular functions, such as cell transformation, the synthesis and degradation of extracellular matrix, and the release of fibrotic mediators. Therefore, this article reviews the biological characteristics of miR-15a/16 and the molecular mechanisms and functions of their dysregulation in fibrotic diseases.

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Section: Regulation Of Cell Transformationmentioning

confidence: 99%

The Molecular Mechanisms and Function of miR-15a/16 Dysregulation in Fibrotic Diseases

Wen

Zhang

Zhou

et al. 2022

IJMS

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“…Overexpression of miR-15b or miR-16 in activated PSCs originating from rats resulted in the reduction of BCL-2 mRNA and an increase of apoptosis as shown by increased RNA and protein levels of caspase 3, 8, and 9 [ 110 ]. In vivo studies in rats showed that treatment with HDAC inhibitors (Vorinostat and Trichostatin A) alleviates the fibroinflammatory phenotype of CP as demonstrated by reduced serum levels of IL-6 and TNFα and reduced levels of markers of activated PSCs such as GFAP and α-SMA [ 109 ]. Simultaneously, Vorinostat treatment increased miR-15/miR-16 and induced apoptosis of PSCs.…”

Section: Chronic Pancreatitismentioning

confidence: 99%

“…Simultaneously, Vorinostat treatment increased miR-15/miR-16 and induced apoptosis of PSCs. Overexpression of miR-15/miR-16 decreased SMAD5, TGFβ pathway effector, and BCL-2 [ 109 ] ( Figure 5 ).…”

Section: Chronic Pancreatitismentioning

confidence: 99%

The Role of MicroRNAs in Pancreatitis Development and Progression

Patel

Almanzar

LaComb

et al. 2023

IJMS

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Pancreatitis (acute and chronic) is an inflammatory disease associated with significant morbidity, including a high rate of hospitalization and mortality. MicroRNAs (miRs) are essential post-transcriptional modulators of gene expression. They are crucial in many diseases’ development and progression. Recent studies have demonstrated aberrant miRs expression patterns in pancreatic tissues obtained from patients experiencing acute and chronic pancreatitis compared to tissues from unaffected individuals. Increasing evidence showed that miRs regulate multiple aspects of pancreatic acinar biology, such as autophagy, mitophagy, and migration, impact local and systemic inflammation and, thus, are involved in the disease development and progression. Notably, multiple miRs act on pancreatic acinar cells and regulate the transduction of signals between pancreatic acinar cells, pancreatic stellate cells, and immune cells, and provide a complex interaction network between these cells. Importantly, recent studies from various animal models and patients’ data combined with advanced detection techniques support their importance in diagnosing and treating pancreatitis. In this review, we plan to provide an up-to-date summary of the role of miRs in the development and progression of pancreatitis.

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“…In addition, miR-31 promotes epithelial regeneration via the Wnt and Hippo signaling pathways [ 66 ]. In chronic pancreatitis, upregulated miR-15 and miR-16 expression can alleviate apoptosis and fibrosis by targeting both BCL-2 and SMAD5 [ 67 ].…”

Section: The Role Of Mirnas In Ccamentioning

confidence: 99%

The Role of microRNAs in Cholangiocarcinoma

Shi

Morishita

Kobara

et al. 2021

IJMS

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Cholangiocarcinoma (CCA), an aggressive malignancy, is typically diagnosed at an advanced stage. It is associated with dismal 5-year postoperative survival rates, generating an urgent need for prognostic and diagnostic biomarkers. MicroRNAs (miRNAs) are a class of non-coding RNAs that are associated with cancer regulation, including modulation of cell cycle progression, apoptosis, metastasis, angiogenesis, autophagy, therapy resistance, and epithelial–mesenchymal transition. Several miRNAs have been found to be dysregulated in CCA and are associated with CCA-related risk factors. Accumulating studies have indicated that the expression of altered miRNAs could act as oncogenic or suppressor miRNAs in the development and progression of CCA and contribute to clinical diagnosis and prognosis prediction as potential biomarkers. Furthermore, miRNAs and their target genes also contribute to targeted therapy development and aid in the determination of drug resistance mechanisms. This review aims to summarize the roles of miRNAs in the pathogenesis of CCA, their potential use as biomarkers of diagnosis and prognosis, and their utilization as novel therapeutic targets in CCA.

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HDAC inhibitors promote pancreatic stellate cell apoptosis and relieve pancreatic fibrosis by upregulating miR-15/16 in chronic pancreatitis

Cited by 19 publications

References 42 publications

The Molecular Mechanisms and Function of miR-15a/16 Dysregulation in Fibrotic Diseases

The Molecular Mechanisms and Function of miR-15a/16 Dysregulation in Fibrotic Diseases

The Role of MicroRNAs in Pancreatitis Development and Progression

The Role of microRNAs in Cholangiocarcinoma

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