MicroRNA-218-5p as a Potential Target for the Treatment of Human Osteoarthritis

Lü, Jun; Ji, Ming-liang; Zhang, Xuejun; Shi, Peiliang; Wu, Hao; Wang, Chen; Im, Hee-Jeong

doi:10.1016/j.ymthe.2017.08.009

Cited by 50 publications

(41 citation statements)

References 39 publications

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“…Our previous studies have shown that dysregulated miR-98 and miR-193a-3p were involved in IDD 10 , 51 . In addition, our recent study demonstrated that inhibition of endogenous miR-218-5p expression/activity appears to be an attractive approach to OA treatment 52 .…”

Section: Discussionmentioning

confidence: 99%

Preclinical development of a microRNA-based therapy for intervertebral disc degeneration

et al. 2018

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Understanding the molecular mechanisms regulating the maintenance and destruction of intervertebral disc may lead to the development of new therapies for intervertebral disc degeneration (IDD). Here we present evidence from miRNA microarray analyses of clinical data sets along with in vitro and in vivo experiments that miR-141 is a key regulator of IDD. Gain- and loss-of-function studies show that miR-141 drives IDD by inducing nucleus pulposus (NP) apoptosis. Furthermore, miR-141 KO in mice attenuated spontaneous and surgically induced IDD. Mechanistically, miR-141 promotes IDD development by targeting and depleting SIRT1, a negative regulator of NF-κB pathway. Therapeutically, upregulation or downregulation of miR-141 by nanoparticle delivery in IDD model aggravated or alleviated experimental IDD, respectively. Our findings reveal a novel mechanism by which miR-141, in part, promotes IDD progression by interacting with SIRT1/NF-κB pathway. Blockade of miR-141 in vivo may serve as a potential therapeutic approach in the treatment of IDD.

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Section: Discussionmentioning

confidence: 99%

Preclinical development of a microRNA-based therapy for intervertebral disc degeneration

et al. 2018

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“…The activation of the Ras/Erk and PI3K/AKT signaling pathways often promotes cancer cell growth and metastasis as well as enhances chemoresistance by inducing c-Myc-mediated cell cycle and EMT signaling. [47][48][49][50][51] Based on Funrich analysis, 52 these two pathways were screened as potential signals affected by miR-296-3p. We confirmed that miR-296-3p suppresses Ras/Erk and PI3K/AKT signals.…”

Section: Discussionmentioning

confidence: 99%

miR-296-3p Negatively Regulated by Nicotine Stimulates Cytoplasmic Translocation of c-Myc via MK2 to Suppress Chemotherapy Resistance

Deng

Liu

et al. 2018

Molecular Therapy

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This study aimed to identify mechanisms by which microRNA 296-3p (miR-296-3p) functions as a tumor suppressor to restrain nasopharyngeal carcinoma (NPC) cell growth, metastasis, and chemoresistance. Mechanistic studies revealed that miR-296-3p negatively regulated by nicotine directly targets the oncogenic protein mitogen-activated protein kinase-activated protein kinase-2 (Mapkapk2) (MK2). Suppression of MK2 downregulated Ras/Braf/Erk/Mek/c-Myc and phosphoinositide-3-kinase (PI3K)/Akt/c-Myc signaling and promoted cytoplasmic translocation of c-Myc, which activated miR-296-3p expression by a feedback loop. This ultimately inhibited cell cycle progression, epithelial-to-mesenchymal transition (EMT), and chemoresistance of NPC. In addition, nicotine as a key component of tobacco was observed to suppress miR-296-3p and thus elevate MK2 expression by inducing PI3K/Akt/c-Myc signaling. In clinical samples, reduced miR-296-3p as an unfavorable factor was inversely correlated with MK2 and c-Myc expression. These results reveal a novel mechanism by which miR-296-3p negatively regulated by nicotine directly targets MK2-induced Ras/Braf/Erk/Mek/c-Myc or PI3K/AKT/c-Myc signaling to stimulate its own expression and suppress NPC cell proliferation and metastasis. miR-296-3p may thus serve as a therapeutic target to reverse chemotherapy resistance of NPC.

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“…For example, the dysregulation of miR-140-3p and miR-140-5p in synovial fluid correlates with the severity of OA [ 16 ]. miR-218-5p is a novel inducer of cartilage destruction via modulation of PI3K/Akt/mTOR signaling, inhibition of endogenous miR-218-5p expression/activity appears to be an attractive approach to OA treatment [ 17 ]. Recent study has described that miR-15a-5p promotes the degeneration of chondrocytes by targeting parathyroid hormone-related protein and may be a potential biomarker of OA [ 18 ].…”

Section: Introductionmentioning

confidence: 99%

MicroRNA-197 regulates chondrocyte proliferation, migration, and inflammation in pathogenesis of osteoarthritis by targeting EIF4G2

et al. 2020

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Recent studies have demonstrated that microRNAs (miRNAs) are involved in many pathological conditions including osteoarthritis (OA). In this study, we aimed to investigate the role of miR-197 in OA and the potential molecular mechanism. The expression levels of miR-197 was detected by quantitative real-time PCR analysis. Cell proliferation and migration abilities were performed by MTT and transwell assays. The concentrations of inflammatory cytokines, including IL-1β, IL-6, and TNF-α, were detect using ELISA assay. Furthermore, luciferase reporter and rescue assays were applied to identify the functional target gene of miR-197 in OA. The results showed that miR-197 expression was significantly downregulated in the OA cartilage tissues compared with normal cartilage tissues, accompanied by upregulation of EIF4G2 expression. An inverse correlation was found between EIF4G2 and miR-197 expressions in OA cartilage tissues. Treatment with miR-197 mimics promoted the growth and migration abilities of chondrocytes, while miR-197 inhibitors induced the opposite effects. Furthermore, restoration of miR-197 significantly decreased IL-1β, IL-6, and TNF-α expression, whereas knockdown of miR-197 led to a induction in these inflammatory mediators. Moreover, EIF4G2 was predicted and confirmed as a directly target of miR-197. Overexpressed miR-197 could downregulate EIF4G2 expression in chondrocytes, while miR-197 knockdown could elevate EIF4G2 expression. Additionally, EIF4G2 overexpression reversed the effects of miR-197 mimics on chondrocytes proliferation, migration and inflammation. Taken together, our study demonstrated that miR-197 promotes chondrocyte proliferation, increases migration, and inhibits inflammation in the pathogenesis of OA by targeting EIF4G2, indicating the potential therapeutic targets of the miR-197/EIF4G2 axis for OA treatment.

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MicroRNA-218-5p as a Potential Target for the Treatment of Human Osteoarthritis

Cited by 50 publications

References 39 publications

Preclinical development of a microRNA-based therapy for intervertebral disc degeneration

Preclinical development of a microRNA-based therapy for intervertebral disc degeneration

miR-296-3p Negatively Regulated by Nicotine Stimulates Cytoplasmic Translocation of c-Myc via MK2 to Suppress Chemotherapy Resistance

MicroRNA-197 regulates chondrocyte proliferation, migration, and inflammation in pathogenesis of osteoarthritis by targeting EIF4G2

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