Paeonol Suppresses Chondrosarcoma Metastasis through  Up-Regulation of miR-141 by Modulating PKCδ and c-Src Signaling Pathway

Horng, Chi‐Ting; Shieh, Pochuen; Tan, Tzu-Wei; Yang, Wei-Hung; Tang, Chih‐Hsin

doi:10.3390/ijms150711760

Cited by 32 publications

(27 citation statements)

References 42 publications

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“…Besides, Ying et al reported that PAE exercises its protective effects on renal injury in diabetic nephropathy rats (Y. Chen et al, ). In addition, accumulating evidence indicated that PAE upregulated several miRs, such as miR‐1 and miR‐142 (Horng et al, ; J. Wu et al, ), which is consistent with our result that PAE increased miR‐124 expression. Furthermore, our results showed that downregulated lncRNA HOTAIR inhibited RIF by downregulating Notch1 through upregulation of miR‐124.…”

Section: Discussionsupporting

confidence: 93%

Paeonol reverses promoting effect of the HOTAIR/miR‐124/Notch1 axis on renal interstitial fibrosis in a rat model

Zhou

Qiu

Yü

et al. 2019

Journal Cellular Physiology

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Renal interstitial fibrosis (RIF) is a common manifestation of inflammatory and noninflammatory renal diseases, which correlates to renal excretory dysfunction. Recently, the long noncoding RNAs (lncRNAs) have been demonstrated to be involved in the development of various renal diseases. Here, we aim to determine whether paeonol (PAE) affects RIF with involvement of the lncRNA HOX transcript antisense intergenic RNA (HOTAIR)/microRNA‐124 (miR‐124)/Notch1 axis. RIF rat models were established by performing unilateral ureteral occlusion (UUO), in which interactions between HOTAIR, Notch1, and miR‐124 were determined. To identify the roles of PAE and HOTAIR in RIF, rats were injected with HOTAIR or PAE. Subsequently, to further investigate the underlying mechanism of PAE in RIF, epithelial to mesenchymal transition (EMT)‐ and migration‐related genes in NRK‐49F cells were measured. Next, rats were further treated with IMR‐1 (inhibitor of the Notch1/Jagged1 signaling pathway) to determine how PAE influences the Notch1/Jagged1 signaling pathway. HOTAIR interacted with miR‐124, and miR‐124 directly targeted Notch1, and HOTAIR was observed to be upregulated in RIF rats. PAE was found to decrease HOTAIR and Notch1 expression but to increase the miR‐124 expression in RIF rats. PAE inhibited EMT and migration of NRK‐49F cells facilitated by HOTAIR. HOTAIR activated the Notch1/Jagged1 signaling pathway by downregulating miR‐124, while PAE reversed these effects of HOTAIR on the Notch1/Jagged1 signaling pathway. Overall, our study demonstrates the contributory effect of lncRNA HOTAIR on RIF by activating the Notch1/Jagged1 signaling pathway via inhibition of miR‐124, whereas administration of PAE can alleviate the effects of HOTAIR on RIF.

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Section: Discussionsupporting

confidence: 93%

Paeonol reverses promoting effect of the HOTAIR/miR‐124/Notch1 axis on renal interstitial fibrosis in a rat model

Zhou

Qiu

Yü

et al. 2019

Journal Cellular Physiology

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“…The effect of Src on the metastasis of osteosarcoma cells is therefore controversial. A number of studies reported that inhibition of c-Src signaling was able to reduce metastasis of chondrosarcoma (57,58). Other studies found that Src inhibition could overcome chemoresistance to induce apoptosis and to inhibit migration (59).…”

Section: Src In Sarcoma Invasion and Metastasismentioning

confidence: 99%

The importance of Src signaling in sarcoma

et al. 2015

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Abstract. Src is a tyrosine kinase that is of significance in tumor biology. The present review focuses on Src, its molecular structure, and role in cancer, in addition to its expression and function in sarcoma. In addition, the feasibility of Src as a potential drug target for the treatment of sarcoma is also discussed. Previous studies have suggested that Src has essential functions in cell proliferation, apoptosis, invasion, metastasis and the tumor microenvironment. Thus, it may be a potential target for cancer therapy. Src has been found to enhance proliferation, reduce apoptosis and promote metastasis in certain subtypes of sarcoma, including osteosarcoma, chondrosarcoma and Ewing's sarcoma. Furthermore, a number of novel effective therapeutic agents, such as SI-83, which target Src have been investigated in vitro and in vivo. Bosutinib and dasatinib, which inhibit Src, have been approved by the U.S. Food and Drug Administration for the treatment of chronic myelogenous leukemia. In addition, vandetanib is approved for the treatment of medullary thyroid cancer. Furthermore, the Src inhibitor, saracatinib, is currently in clinical trials for the treatment of a variety of solid tumors, including breast and lung cancers. Thus, Src is considered to be an important factor in sarcoma progression and may present a novel clinical therapeutic target. This review demonstrates the importance and clinical relevance of Src in sarcoma, and discusses a number of small molecular inhibitors of src kinase, such as dasatinib and sarcatinib, which are currently in clinical trials for the treatment of sarcoma patients.

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“…Chondrosarcoma is one of malignant bone tumors and has a tendency of local invasion and distant metastasis [106]. A traditional Chinese remedy named Paeonol (2'-hydroxy-4'-methoxyacetophenone) was proved to be capable of inhibiting chondrosarcoma cell migration and invasion though upregulation of miR-141 via PKC and c-Src pathways [107].…”

Section: Mir-141 and Tumor Invasion And Metastasismentioning

confidence: 99%

The Roles of MicroRNA-141 in Human Cancers: From Diagnosis to Treatment

Gao

Feng²,

Han³

et al. 2016

Cell Physiol Biochem

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Cancer remains one of the most threatening causes of human health impairment, and the mechanisms underlying tumorigenesis have not been completely characterized. MicroRNAs (miRNAs) are a group of endogenous, small (18∼25 nucleotides) non-coding RNAs which negatively regulate gene expressions by directly binding to the 3'-untranslated regions (3'-UTRs) of the target messenger RNAs (mRNAs). Increasing evidence has demonstrated abnormal miRNA profiles and confirmed their involvement in tumor initiation and progression. As one important member of the miR-200 family, microRNA (miR)-141 is aberrantly expressed in many human malignant tumors, participating in various cellular processes including epithelial-mesenchymal transition (EMT), proliferation, migration, invasion, and drug resistance. In the present review, we briefly describe the mechanisms underlying miR-141-mediated tumorigenesis and the possible future of miR-141 as a potential diagnostic and prognostic parameter as well as therapeutic target in clinical applications.

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Paeonol Suppresses Chondrosarcoma Metastasis through Up-Regulation of miR-141 by Modulating PKCδ and c-Src Signaling Pathway

Cited by 32 publications

References 42 publications

Paeonol reverses promoting effect of the HOTAIR/miR‐124/Notch1 axis on renal interstitial fibrosis in a rat model

Paeonol reverses promoting effect of the HOTAIR/miR‐124/Notch1 axis on renal interstitial fibrosis in a rat model

The importance of Src signaling in sarcoma

The Roles of MicroRNA-141 in Human Cancers: From Diagnosis to Treatment

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