miR-21 promotes proliferation and inhibits apoptosis of hepatic stellate cells through targeting PTEN/PI3K/AKT pathway

Hao, Xinjie; Xu, Chengzhen; Wang, Jintai; Li, Xiaojie; Wang, Ming-Min; Yi-hai, GU; Liang, Zhigang

doi:10.1080/10799893.2019.1585452

Cited by 29 publications

(23 citation statements)

References 21 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Moreover, miR-21-5p might protect monocyte from IHR-induced cell apoptosis and cytotoxicity by inhibiting TLR4/TNF-α/IL-6R-mediated inflammation. In line with our findings, previous studies have shown that miR-21 has anti-inflammatory and anti-apoptosis effects by inhibiting NF-κB-TNF-α-TLR and PDCD4-caspase-3 pathways, respectively, while TNF-α can suppress miR-21 functional axis [16][17][18]20,25,29,36]. The results open the possibility of using miR-21-5p mimic to overcome systemic inflammation and improve outcomes in OSA patients.…”

Section: Discussionsupporting

confidence: 91%

“…Previous studies have shown that miR-21 can inhibit cardiac myocyte/hepatic stellate cell apoptosis through PTEN/PI3K/Akt pathway, protect against neuronal cell death through FasL signaling, attenuate angiogenesis through SMAD7 signaling, and suppress secretion of inflammatory cytokines and chemokine receptor type 7 under hypoxia conditions, whereas it may contribute to pulmonary hypertension through inhibiting DDAH1 and RhoB under hyoxia [24][25][26][27][28]. Recently, miR-21 has been demonstrated to protect IHR or ischemia-reperfusion injury to islet cell, hepatocyte, nucleus pulposus cell, cardiac cells, and kidney epithelial cell via inhibiting PTEN/PI3K/AKT signaling pathway [29][30][31][32].…”

Section: Discussionmentioning

confidence: 99%

“…To investigate the protective effect of miR-21-5p on overt inflammation and cell injury, we first evaluated whether miR-21-5p mimic had inhibitory effects on several predicted target genes in THP-1 cells under NOX condition. miR-21-5p mimic at different concentrations(1,5,10,25, and 50 nM, respectively) enhanced miR-21-5p gene expressions(Figure 3a, versus 0 nM, all p-values < 0.05) in a dose-dependent manner, while inhibited TNF-α (Figure 3b, versus 0 nM, all p-values < 0.05), IL-6R (Figure 3c, versus 0 nM, all p-values < 0.05), and TLR4 (Figure 3d, versus 0 nM, all p-values < 0.05) gene expressions in a dose-dependent manner.…”

mentioning

confidence: 99%

See 2 more Smart Citations

miR-21-5p Under-Expression in Patients with Obstructive Sleep Apnea Modulates Intermittent Hypoxia with Re-Oxygenation-Induced-Cell Apoptosis and Cytotoxicity by Targeting Pro-Inflammatory TNF-α-TLR4 Signaling

Chen

Hsu

et al. 2020

IJMS

View full text Add to dashboard Cite

The purpose of this study is to explore the anti-inflammatory role of microRNAs (miR)-21 and miR-23 targeting the TLR/TNF-α pathway in response to chronic intermittent hypoxia with re-oxygenation (IHR) injury in patients with obstructive sleep apnea (OSA). Gene expression levels of the miR-21/23a, and their predicted target genes were assessed in peripheral blood mononuclear cells from 40 treatment-naive severe OSA patients, and 20 matched subjects with primary snoring (PS). Human monocytic THP-1 cell lines were induced to undergo apoptosis under IHR exposures, and transfected with miR-21-5p mimic. Both miR-21-5p and miR-23-3p gene expressions were decreased in OSA patients as compared with that in PS subjects, while TNF-α gene expression was increased. Both miR-21-5p and miR-23-3p gene expressions were negatively correlated with apnea hypopnea index and oxygen desaturation index, while TNF-α gene expression positively correlated with apnea hypopnea index. In vitro IHR treatment resulted in decreased miR-21-5p and miR-23-3p expressions. Apoptosis, cytotoxicity, and gene expressions of their predicted target genes-including TNF-α, ELF2, NFAT5, HIF-2α, IL6, IL6R, EDNRB, and TLR4-were all increased in response to IHR, while all were reversed with miR-21-5p mimic transfection under IHR condition. The findings provide biological insight into mechanisms by which IHR-suppressed miRs protect cell apoptosis via inhibit inflammation, and indicate that over-expression of the miR-21-5p may be a new therapy for OSA.

show abstract

Section: Discussionsupporting

confidence: 91%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

See 1 more Smart Citation

miR-21-5p Under-Expression in Patients with Obstructive Sleep Apnea Modulates Intermittent Hypoxia with Re-Oxygenation-Induced-Cell Apoptosis and Cytotoxicity by Targeting Pro-Inflammatory TNF-α-TLR4 Signaling

Chen

Hsu

et al. 2020

IJMS

View full text Add to dashboard Cite

show abstract

“…We also demonstrated that miR-21 represents one of the most abundant miRs transported within EV cargos secreted by oral cancer cells and that CSC_EVs contained a significantly higher level of miR-21 than their parental counterparts. This is of translational relevance, considering that miR-21 is a well-established oncogenic miR whose major targets include the tumor suppressors PTEN and PDCD4 [30,31], both of which inhibit PI3K/AKT/mTOR signaling and the Wnt/β-catenin cascade [30,32]. Moreover, EV miR-21 was implicated in resistance of recipient cancer cells to anticancer therapeutics [12,33]; in agreement, our bioinformatics analysis showed that miR-21 was the most abundant miR encapsulated within salivary EVs from six patients with OSCC.…”

Section: Discussionmentioning

confidence: 99%

Ovatodiolide Suppresses Oral Cancer Malignancy by Down-Regulating Exosomal Mir-21/STAT3/β-Catenin Cargo and Preventing Oncogenic Transformation of Normal Gingival Fibroblasts

Chen

Bamodu

et al. 2019

Cancers

View full text Add to dashboard Cite

Oral squamous cell carcinoma (OSCC) is among the most commonly diagnosed malignancies in the world. Patients with OSCC often develop treatment resistance, resulting in a poor prognosis. Mounting evidence indicates that interactions between cancerous cells and other components of the tumor microenvironment (TME) determine their response to treatment. Herein, we examined the role of cancer stem cell-derived extracellular vesicles (CSC_EVs) generated from CAL27 and SCC-15 OSCC cells in the development of cisplatin (CDDP) resistance. We demonstrated that CSC_EVs enhance CDDP resistance, clonogenicity, and the tumorsphere formation potential of OSCC cells. Our bioinformatics analyses revealed that OSCC_EVs are enriched with microRNA (miR)-21-5p and are associated with increased metastasis, stemness, chemoresistance, and poor survival in patients with OSCC. Mechanistically, enhanced activity of CSC_EVs was positively correlated with upregulated Cancers 2020, 12, 56 2 of 16 β-catenin, phosphatidylinositol-3 kinase (PI3K), signal transducer and activator of transcription 3 (STAT3), mammalian target of rapamycin (mTOR), and transforming growth factor (TGF)-β1 messenger (m)RNA and protein expression levels. CSC_EVs also conferred a cancer-associated fibroblast (CAF) phenotype on normal gingival fibroblasts (NGFs), with the resultant CAFs enhancing the oncogenicity of OSCC cells. Interestingly, treatment with ovatodiolide (OV), the bioactive component of Anisomeles indica, suppressed OSCC tumorigenesis by reducing the cargo content of EVs derived from CSCs, suppressing self-renewal, and inhibiting the NGF-CAF transformation by disrupting EV-TME interactions. Moreover, by suppressing miR-21-5p, STAT3, and mTOR expressions in CSC_EVs, OV re-sensitized CSCs to CDDP and suppressed OSCC tumorigenesis. In vivo, treatment with OV alone or in combination with CDDP significantly reduced the tumor sphere-forming ability and decreased EV cargos containing mTOR, PI3K, STAT3, β-catenin, and miR-21-5p. In summary, our findings provide further strong evidence of OV's therapeutic effect in OSCC.

show abstract

“…In a murine glioma model, miR‐26a mediated PTEN repression enhances de novo tumour formation 33 ; Duan et.al proved that miR‐498 promotes proliferation, migration and invasion of prostate cancer cells and decreases radiation sensitivity by targeting PTEN 34 . Hao et al proved miR‐21 promotes proliferation and inhibits apoptosis of HSC through targeting PTEN/PI3K/Akt pathway 35 . These results demonstrate that PTEN was regulated by different kinds of miRNAs and influenced cell biological functions.…”

Section: Discussionmentioning

confidence: 99%

Identification lncRNA LOC102551149/miR‐23a‐5p pathway in hepatic fibrosis

Zhao

et al. 2020

Eur J Clin Investigation

View full text Add to dashboard Cite

Background: Hepatic fibrosis is a worldwide incurable disease; due to the complex and unclear mechanism, there lack the effective therapeutic targets. However, the mechanism of miR-23a-5p underling this pathological process is largely not clear.The purpose of this study was to investigate the role of miR-23a-5p in hepatic fibrosis and HSC activation. Methods: The content of miR-23a-5p in hepatic fibrosis induced by Nnitrosodimethylamine (NDMA) and HSC activation induced by platelet-derived growth factor (PDGF) was detected by qRT-PCR. H&E staining, Masson staining and Shear wave electrography (SWE) were used to detect the degree of hepatic fibrosis. Immunohistochemistry staining, qRT-PCR and Western blot detect the related markers of liver fibrosis or HSC activation, as well as the related pathway genes and proteins. Dual-luciferase reporter system verifies the interaction between miR-23a-5p with PTEN or miR-23a-5p with lncRNA LOC102551149 in HSC-T6. siRNA and miRNA mimic transfer to HSC-T6 to detect the function of lncRNA LOC102551149 and miR-23a-5p on HSC activation. Results: After hepatic fibrosis and HSC activation happened, the expression of miR-23a-5p was up-regulated, whereas anti-miR-23a-5p can alleviate hepatic fibrosis and HSC activation. Further research shows miR-23a-5p can target PTEN and degrade it, causing activation of PI3K/Akt/mTOR/Snail pathway. lncRNA LOC102551149 can be used as a competition endogenous RNA (ceRNA) targeting miR-23a-5p through base pairing, and siRNA LOC102551149 or exogenous miR-23a-5p can induce HSC activation through PI3K/Akt/mTOR/Snail pathway. Conclusion: We demonstrate mechanism pathway of miR-23a-5p on hepatic fibrosis and HSC activation, which may develop a therapeutic target for hepatic fibrosis. K E Y W O R D S hepatic fibrosis, HSC activation, lncRNA LOC102551149, miR-23a-5p, PI3K/Akt, PTEN 2 of 14 | DONG et al.

show abstract

miR-21 promotes proliferation and inhibits apoptosis of hepatic stellate cells through targeting PTEN/PI3K/AKT pathway

Cited by 29 publications

References 21 publications

miR-21-5p Under-Expression in Patients with Obstructive Sleep Apnea Modulates Intermittent Hypoxia with Re-Oxygenation-Induced-Cell Apoptosis and Cytotoxicity by Targeting Pro-Inflammatory TNF-α-TLR4 Signaling

miR-21-5p Under-Expression in Patients with Obstructive Sleep Apnea Modulates Intermittent Hypoxia with Re-Oxygenation-Induced-Cell Apoptosis and Cytotoxicity by Targeting Pro-Inflammatory TNF-α-TLR4 Signaling

Ovatodiolide Suppresses Oral Cancer Malignancy by Down-Regulating Exosomal Mir-21/STAT3/β-Catenin Cargo and Preventing Oncogenic Transformation of Normal Gingival Fibroblasts

Identification lncRNA LOC102551149/miR‐23a‐5p pathway in hepatic fibrosis

Contact Info

Product

Resources

About