MicroRNA-99a inhibits insulin-induced proliferation, migration, dedifferentiation, and rapamycin resistance of vascular smooth muscle cells by inhibiting insulin-like growth factor-1 receptor and mammalian target of rapamycin

Zhang, Ziwei; Guo, R. S.; Lv, Jian; Wang, Xianmei; Ye, Jinshan; Lu, Nihong; Lü, Xing; Yang, Lixia

doi:10.1016/j.bbrc.2017.03.056

Cited by 20 publications

(14 citation statements)

References 36 publications

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“…Moreover, reducing drug resistance in breast cancer plays a positive role in treatment 75 . Other studies have also confirmed the inhibitory effect of miR-15, miR-16, and miR-99a in breast cancer 76 - 78 .…”

Section: Mtor Signaling Pathway and Cancersmentioning

confidence: 67%

mTOR signaling-related MicroRNAs and Cancer involvement

et al. 2018

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MicroRNAs (miRNAs) are a class of single-stranded RNAs, 18-23 nucleotides in length that regulate gene expression at the post-transcriptional level. Dysregulation of miRNAs has been closely associated with the development of cancer. In the process of tumorigenesis, mammalian target of rapamycin (mTOR) plays important roles, and the mTOR signaling pathway is aberrant in various types of human cancers, including non-small cell lung cancer (NSCLC), breast cancer, prostate cancer, as well as others. However, the relationship between miRNAs and the mTOR signaling pathway is indistinct. Herein, we not only summarize the progress of miRNAs and the mTOR signaling pathway in cancers, but also highlight their role in the diagnosis and treatment in the clinic.

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Section: Mtor Signaling Pathway and Cancersmentioning

confidence: 67%

mTOR signaling-related MicroRNAs and Cancer involvement

et al. 2018

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“…Accordingly, miR-100 was suggested to modulate IGFR and mTOR and to mediate adipogenesis. Another miRNA was proposed to play an important role in the pathogenesis of DM is miR-99a, which was suggested to promote insulin-induced proliferation, migration and phenotypeconversion of vascular smooth muscle cells, at least in part, by the inhibition of IGFR-1 mTOR signaling [31]. Hence, miR-7a may act as an mTOR-regulating brake on adult ß-cell proliferation, which is a critical factor in regenerative therapeutic approaches for DM.…”

Section: Discussionmentioning

confidence: 99%

MicroRNA-496 and Mechanistic Target of Rapamycin Expression are Associated with Type 2 Diabetes Mellitus and Obesity in Elderly People

et al. 2019

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Background: Mechanistic target of rapamycin (mTOR) regulates lipid and glucose metabolism thus playing a key role in metabolic diseases like type 2 diabetes mellitus (T2DM). Recently, we demonstrated a functional interaction of microRNA-496 (miR-496) with mTOR and its impact on the regulation of human ageing. Objectives: As T2DM is most prevalent in older adults, we hypothesized that miR-496 may also have an impact on mTOR regulation in T2DM. Methods: Based on real-time PCR and enzyme-linked immunosorbent assay, mTOR gene and protein expression as well as miR-496 expression were monitored in peripheral blood mononuclear cells (PBMC) from T2DM patients (median age: 71) and healthy age- and BMI matched controls (median age: 69). Results: We demonstrated significant upregulation of phospho-mTOR and P70S6 Kinase (P70S6K) levels and significant downregulation of miR-496 in PBMC from elderly T2DM patients in comparison to a BMI and age-matched control cohort. Moreover, significant upregulation of phospho-mTOR protein and significant downregulation of miR-496 were observed in advanced stages of obesity. Conclusions: BMI-dependent upregulation of mTOR and the inverse expression profile of miR-496 observed in elderly T2DM patients suggest a correlation with T2DM. Hence, our results indicate a potential association of miR-496 with mTOR expression in elderly T2DM patients and obesity. Since phosphorylation of P70S6K was also elevated in T2DM patients, we conclude that mTOR signaling through TORC1 may be affected in the regulation of T2DM.

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“…[16] PDGF treatment was also associated with enhanced migration and proliferation of VSMCs [16]. Likewise, rapamycin, an inducer of autophagy activation, is capable of inhibiting both cell proliferation and migration [17,18]. Consequently, due to the crucial role of rapamycin-induced autophagy in VSMC function, rapamycin-based drugs have been used in drugeluting stents to prevent restenosis after percutaneous coronary intervention.…”

Section: Ivyspringmentioning

confidence: 99%

EHMT2/G9a Inhibits Aortic Smooth Muscle Cell Death by Suppressing Autophagy Activation

Chen¹,

Hu²,

Huo³

et al. 2020

Int. J. Biol. Sci.

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Although EHMT2 (also known as G9a) plays a critical role in several kinds of cancers and cardiac remodeling, its function in vascular smooth muscle cells (VSMCs) remains unknown. In the present study, we revealed a novel function of EHMT2 in regulating autophagic cell death (ACD) of VSMC. Inhibition of EHMT2 by BIX01294 or knockdown of EHMT2 resulted in reduced VSMC numbers which were independent of proliferation and apoptosis. Interestingly, EHMT2 protein levels were significantly decreased in VSMCs treated with autophagic inducers. Moreover, more autophagic vacuoles and accumulated LC3II were detected in VSMCs treated with BIX01294 or lenti-shEHMT2 than their counterparts. Furthermore, we found that EHMT2 inhibited the ACD of VSMCs by suppressing autophagosome formation. Mechanistically, the pro-autophagic effect elicited by EHMT2 inhibition was associated with SQSTM1 and BECN1 overexpression. Moreover, these detrimental effects were largely nullified by SQSTM1 or BECN1 knockdown. More importantly, similar results were observed in primary human aortic VSMCs. Overall, these findings suggest that EHMT2 functions as a crucial negative regulator of ACD via decreasing SQSTM1 or BECN1 expression and that EHMT2 could be a potent therapeutic target for cardiovascular diseases (e.g., aortic dissection).

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MicroRNA-99a inhibits insulin-induced proliferation, migration, dedifferentiation, and rapamycin resistance of vascular smooth muscle cells by inhibiting insulin-like growth factor-1 receptor and mammalian target of rapamycin

Cited by 20 publications

References 36 publications

mTOR signaling-related MicroRNAs and Cancer involvement

mTOR signaling-related MicroRNAs and Cancer involvement

MicroRNA-496 and Mechanistic Target of Rapamycin Expression are Associated with Type 2 Diabetes Mellitus and Obesity in Elderly People

EHMT2/G9a Inhibits Aortic Smooth Muscle Cell Death by Suppressing Autophagy Activation

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