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Inhibition of microRNA-128-3p attenuates hypercholesterolemia in mouse model

Chandra, Amit, Sharma, Kritika, Pratap, Kunal, Singh, Vijaypal, Saini, Neeru·2021·Life Sciences
DOI 10.1016/j.lfs.2020.118633
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Abstract

Aims Hypercholesterolemia remains a critical risk factor for cardiovascular diseases and there is an urgent need to develop effective alternative therapeutics. Herein, we investigated the effects of miR-128-3p inhibition on serum cholesterol levels using a hypercholesterolemic mouse model. Materials and methods Five injections of anti-miR-128-3p (AM-128) treatment were given, and the cholesterol profile in serum and liver was quantified. We validated the underlying gene network using qRT-PCR, western blotting, ELISA, and dual luciferase assays. Key findings AM-128 treatment inhibits cholesterol biosynthesis by upregulating INSIG1 and downregulating HMGCR (3-hydroxy-3-methylglutaryl-CoA reductase) expression. The serum cholesterol clearance by SR-B1 (scavenger receptor class B member 1) and LDLR (low density lipoprotein receptors) was also increased. Furthermore, the catabolism of cholesterol by CYP7A1 (cytochrome P450 family 7 subfamily A member 1) was increased. Significance Our results confirmed a critical role of miR-128-3p inhibition in lowering serum cholesterol and suggest its potential therapeutic implications in reversing hypercholesterolemia.

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  • Inhibition of miR-128-3p increases hepatic LDLR abundance and reduces plasma LDL-cholesterol in mice.

    “as was the case with inhibition of miR-128-3p [48].”

    From The low-density lipoprotein receptor: Emerging post-transcriptional regulatory mechanisms (2025) · cites this paper as [48]

  • Numerous miRNAs directly bind LDLR mRNA 3′UTR and decrease its expression, including miR-27a, miR-27b, miR-128-1, miR-128-3p, miR-130b, miR-148a, miR-184a, miR-185, and miR-301b.

    “Numerous miRNAs have been shown to directly bind LDLR mRNA 3' UTR and decrease its expression (Fig. 2), including miR-27a, miR-27b, miR-128-1, miR-128-3p, miR-130b, miR-148a, miR-184a, miR-185, and miR-301b [43][44][45][46][47][48].”

    From The low-density lipoprotein receptor: Emerging post-transcriptional regulatory mechanisms (2025) · cites this paper as [48]

  • miR-27a, miR-27b, miR-128-1, miR-128-3p, miR-130b, miR-148a, miR-184a, miR-185, and miR-301b inhibit expression of the LDLR, decreasing LDLR.

    “miR-27a, miR-27b, miR-128-1, miR-128-3p, miR-130b, miR-148a, miR-184a, miR-185, miR-301b Inhibit expression of the LDLR ↓ [43-48]”

    From The low-density lipoprotein receptor: Emerging post-transcriptional regulatory mechanisms (2025) · cites this paper as [48]

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Metadata

Authors
Chandra, A., Sharma, K., Pratap, K., Singh, V., & Saini, N.
Venue
Life Sciences
Publisher
Elsevier BV
Published
2021-01
Volume
264
Pages
118633
ISSN
0024-3205
DOI
10.1016/j.lfs.2020.118633
Cited by
19
References
1
Language
en
Licence
Funders
Department of Biotechnology, Ministry of Science and Technology, India

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