Novel efficacious microRNA-30c analogs reduce apolipoprotein B secretion in human hepatoma and primary hepatocyte cells

Yadav, Pradeep Kumar; Haruehanroengra, Phensinee; Irani, Sarah; Wang, Ting; Ansari, Abulaish; Sheng, Jia; Hussain, M. Mahmood

doi:10.1016/j.jbc.2022.101813

Cited by 7 publications

(9 citation statements)

References 47 publications

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“…Human hepatoma Huh-7 cells express apoB and MTP and secrete apoB-containing lipoproteins similar to HepG2 cells ( 31 ). We have recently used these cells to identify microRNA-30c analogs that reduce MTP expression ( 32 ). In our experience, these cells are easier to transfect than HepG2 cells.…”

Section: Resultsmentioning

confidence: 99%

Generation of hepatoma cell lines deficient in microsomal triglyceride transfer protein

Anaganti

Chattopadhyay²,

Poirier³

et al. 2022

Journal of Lipid Research

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Section: Resultsmentioning

confidence: 99%

Generation of hepatoma cell lines deficient in microsomal triglyceride transfer protein

Anaganti

Chattopadhyay²,

Poirier³

et al. 2022

Journal of Lipid Research

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“…The blots were imaged using ChemiDoc TM touch imaging system. Analysis on western blot also showed a decrease in MTP protein expression (Yadav et al, 2022). 2) by introducing phosphorothioate linkages, which have been suggested to…”

Section: Note: the Synthesis Of Galnac-modified Rna Strands Begins Wi...mentioning

confidence: 93%

“…Compared to the native miR-30c-1-3p annealed with miR-30c-5p, the modified duplexes showed an overall increase in thermal stability by approximately 7 °C, indicating enhanced duplex stability (A). The CD spectra showed similar conformation indicating that the modification of miR-30c-1-3p does not impair the interaction with the miR-30c-5p (B)(Yadav et al, 2022).…”

mentioning

confidence: 88%

“…We have previously reported that miR-30c interacts with the 3′-untranslated region of the MTP mRNA, leading to mRNA degradation and thereby reducing the secretion of apolipoprotein B by liver cells (James Soh, 2018). The successful synthesis of modified miR-30c passenger analogs with increased duplex stability and enhanced uptake by hepatoma cells, resulting in significant ApoB reductions without affecting the level of ApoA1 (Yadav et al, 2022), have proven the feasibility of this approach. By introducing GalNAc residues at either end, we eliminated the need for lipid emulsion delivery as it might be more cost effective.…”

Section: Introductionmentioning

confidence: 99%

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Synthesis of Novel MicroRNA-30c Analogs to Reduce Apolipoprotein B Secretion in Human Hepatoma Cells

Zheng¹,

Haruehanroengra²,

Yadav³

et al. 2022

BIO-PROTOCOL

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Atherosclerosis, a condition characterized by thickening of the arteries due to lipid deposition, is the major contributor to and hallmark of cardiovascular disease. Although great progress has been made in lowering the lipid plaques in patients, the conventional therapies fail to address the needs of those that are intolerant or non-responsive to the treatment. Therefore, additional novel therapeutic approaches are warranted. We have previously shown that increasing the cellular amounts of microRNA-30c (miR-30c) with the aid of viral vectors or liposomes can successfully reduce plasma cholesterol and atherosclerosis in mice. To avoid the use of viruses and liposomes, we have developed new methods to synthesize novel miR-30c analogs with increasing potency and efficacy, including 2'-O-methyl (2'OMe), 2'-fluoro (2'F), pseudouridine (ᴪ), phosphorothioate (PS), and N-acetylgalactosamine (GalNAc). The discovery of these modifications has profoundly impacted the modern RNA therapeutics, as evidenced by their increased nuclease stability and reduction in immune responses. We show that modifications on the passenger strand of miR-30c not only stabilize the duplex but also aid in a more readily uptake by the cells without the aid of viral vectors or lipid emulsions. After uptake, the analogs with PS linkages and GalNAc-modified ribonucleotides significantly reduce the secretion of apolipoprotein B (ApoB) without affecting apolipoprotein A1 (ApoA1) in human hepatoma Huh-7 cells. We envision an enormous potential for these modified miR-30c analogs in therapeutic intervention for treating cardiovascular diseases. Cite as: Zheng, Y. Y. et al. (2022). Synthesis of Novel MicroRNA-30c Analogs to Reduce Apolipoprotein B Secretion in Human Hepatoma Cells. Bio-protocol 12(24): e4574.

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“…Therefore, clinical application of natural miRNAs could be a promising approach for the treatment of some diseases and may potentially enhance the therapeutic effects as compared with siRNAs or other synthetic RNAs ( Rupaimoole and Slack, 2017 ). Interestingly, using miRNAs analogs could increase the half-life and delivery of miRNAs to the target tissues; for example, in miR-30c analog, the passenger strand of miR-30c was modified which leads to stability enhancement and augment its delivery to liver cells ( Yadav et al, 2022 ). Despite the importance and necessity of ncRNAs in preclinical investigations, their efficient and successful utilization in clinical trials has faced hurdles so far.…”

Section: The Challenges and Opportunities Of Rna-based Therapeutics F...mentioning

confidence: 99%

Regulatory Non-Coding RNAs in Familial Hypercholesterolemia, Theranostic Applications

Alikhani

Pourhamzeh

Seydi

et al. 2022

Front. Cell Dev. Biol.

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Familial hypercholesterolemia (FH) is a common monogenic disease which is associated with high serum levels of low-density lipoprotein cholesterol (LDL-C) and leads to atherosclerosis and cardiovascular disease (CVD). Early diagnosis and effective treatment strategy can significantly improve prognosis. Recently, non-coding RNAs (ncRNAs) have emerged as novel biomarkers for the diagnosis and innovative targets for therapeutics. Non-coding RNAs have essential roles in the regulation of LDL-C homeostasis, suggesting that manipulation and regulating ncRNAs could be a promising theranostic approach to ameliorate clinical complications of FH, particularly cardiovascular disease. In this review, we briefly discussed the mechanisms and pathophysiology of FH and novel therapeutic strategies for the treatment of FH. Moreover, the theranostic effects of different non-coding RNAs for the treatment and diagnosis of FH were highlighted. Finally, the advantages and disadvantages of ncRNA-based therapies vs. conventional therapies were discussed.

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Novel efficacious microRNA-30c analogs reduce apolipoprotein B secretion in human hepatoma and primary hepatocyte cells

Cited by 7 publications

References 47 publications

Generation of hepatoma cell lines deficient in microsomal triglyceride transfer protein

Generation of hepatoma cell lines deficient in microsomal triglyceride transfer protein

Synthesis of Novel MicroRNA-30c Analogs to Reduce Apolipoprotein B Secretion in Human Hepatoma Cells

Regulatory Non-Coding RNAs in Familial Hypercholesterolemia, Theranostic Applications

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