Murine Falcor/LL35 lncRNA Contributes to Glucose and Lipid Metabolism In Vitro and In Vivo

Glucose and lipid metabolism are crucial functional systems in eukaryotes. A large number of experimental studies both in animal models and humans have shown that long non-coding RNAs (lncRNAs) play an important role in glucose and lipid metabolism. Previously, human lncRNA DEANR1/linc00261 was desc...

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Main Authors: Evgeniya Shcherbinina, Tatiana Abakumova, Daniil Bobrovskiy, Ilia Kurochkin, Ksenia Deinichenko, Elena Stekolshchikova, Nickolay Anikanov, Rustam Ziganshin, Pavel Melnikov, Ekaterina Khrameeva, Maria Logacheva, Timofei Zatsepin, Olga Sergeeva
Format: Article
Language:English
Published: MDPI AG 2022-06-01
Series:Biomedicines
Subjects:
Online Access:https://www.mdpi.com/2227-9059/10/6/1397
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author Evgeniya Shcherbinina
Tatiana Abakumova
Daniil Bobrovskiy
Ilia Kurochkin
Ksenia Deinichenko
Elena Stekolshchikova
Nickolay Anikanov
Rustam Ziganshin
Pavel Melnikov
Ekaterina Khrameeva
Maria Logacheva
Timofei Zatsepin
Olga Sergeeva
author_facet Evgeniya Shcherbinina
Tatiana Abakumova
Daniil Bobrovskiy
Ilia Kurochkin
Ksenia Deinichenko
Elena Stekolshchikova
Nickolay Anikanov
Rustam Ziganshin
Pavel Melnikov
Ekaterina Khrameeva
Maria Logacheva
Timofei Zatsepin
Olga Sergeeva
author_sort Evgeniya Shcherbinina
collection DOAJ
description Glucose and lipid metabolism are crucial functional systems in eukaryotes. A large number of experimental studies both in animal models and humans have shown that long non-coding RNAs (lncRNAs) play an important role in glucose and lipid metabolism. Previously, human lncRNA DEANR1/linc00261 was described as a tumor suppressor that regulates a variety of biological processes such as cell proliferation, apoptosis, glucose metabolism and tumorigenesis. Here we report that murine lncRNA Falcor/LL35, a proposed functional analog of human DEANR1/linc00261, is predominantly expressed in murine normal hepatocytes and downregulated in HCC and after partial hepatectomy. The application of high-throughput approaches such as RNA-seq, LC-MS proteomics, lipidomics and metabolomics analysis allowed changes to be found in the transcriptome, proteome, lipidome and metabolome of hepatocytes after LL35 depletion. We revealed that LL35 is involved in the regulation of glycolysis and lipid biosynthesis in vitro and in vivo. Moreover, LL35 affects Notch and NF-κB signaling pathways in normal hepatocytes. All observed changes result in the decrease in the proliferation and migration of hepatocytes. We demonstrated similar phenotype changes between murine LL35 and human linc00261 depletion in vitro and in vivo that opens the opportunity to translate results for LL35 from a liver murine model to possible functions of human lncRNA linc00261.
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spelling doaj.art-f6bbbbe636d748dfbab8ceddb29d76a72023-11-23T15:44:05ZengMDPI AGBiomedicines2227-90592022-06-01106139710.3390/biomedicines10061397Murine Falcor/LL35 lncRNA Contributes to Glucose and Lipid Metabolism In Vitro and In VivoEvgeniya Shcherbinina0Tatiana Abakumova1Daniil Bobrovskiy2Ilia Kurochkin3Ksenia Deinichenko4Elena Stekolshchikova5Nickolay Anikanov6Rustam Ziganshin7Pavel Melnikov8Ekaterina Khrameeva9Maria Logacheva10Timofei Zatsepin11Olga Sergeeva12Skolkovo Institute of Science and Technology, 121205 Moscow, RussiaSkolkovo Institute of Science and Technology, 121205 Moscow, RussiaFaculty of Bioengineering and Bioinformatics, Lomonosov Moscow State University, 119234 Moscow, RussiaSkolkovo Institute of Science and Technology, 121205 Moscow, RussiaInstitute of Biomedical Chemistry, 119121 Moscow, RussiaSkolkovo Institute of Science and Technology, 121205 Moscow, RussiaSkolkovo Institute of Science and Technology, 121205 Moscow, RussiaShemyakin-Ovchinnikov Institute of Bioorganic Chemistry, 117997 Moscow, RussiaSerbsky National Medical Research Center for Psychiatry and Narcology, 119034 Moscow, RussiaSkolkovo Institute of Science and Technology, 121205 Moscow, RussiaSkolkovo Institute of Science and Technology, 121205 Moscow, RussiaSkolkovo Institute of Science and Technology, 121205 Moscow, RussiaSkolkovo Institute of Science and Technology, 121205 Moscow, RussiaGlucose and lipid metabolism are crucial functional systems in eukaryotes. A large number of experimental studies both in animal models and humans have shown that long non-coding RNAs (lncRNAs) play an important role in glucose and lipid metabolism. Previously, human lncRNA DEANR1/linc00261 was described as a tumor suppressor that regulates a variety of biological processes such as cell proliferation, apoptosis, glucose metabolism and tumorigenesis. Here we report that murine lncRNA Falcor/LL35, a proposed functional analog of human DEANR1/linc00261, is predominantly expressed in murine normal hepatocytes and downregulated in HCC and after partial hepatectomy. The application of high-throughput approaches such as RNA-seq, LC-MS proteomics, lipidomics and metabolomics analysis allowed changes to be found in the transcriptome, proteome, lipidome and metabolome of hepatocytes after LL35 depletion. We revealed that LL35 is involved in the regulation of glycolysis and lipid biosynthesis in vitro and in vivo. Moreover, LL35 affects Notch and NF-κB signaling pathways in normal hepatocytes. All observed changes result in the decrease in the proliferation and migration of hepatocytes. We demonstrated similar phenotype changes between murine LL35 and human linc00261 depletion in vitro and in vivo that opens the opportunity to translate results for LL35 from a liver murine model to possible functions of human lncRNA linc00261.https://www.mdpi.com/2227-9059/10/6/1397long non-coding RNAlipid metabolismglucose metabolismhepatocyteliver
spellingShingle Evgeniya Shcherbinina
Tatiana Abakumova
Daniil Bobrovskiy
Ilia Kurochkin
Ksenia Deinichenko
Elena Stekolshchikova
Nickolay Anikanov
Rustam Ziganshin
Pavel Melnikov
Ekaterina Khrameeva
Maria Logacheva
Timofei Zatsepin
Olga Sergeeva
Murine Falcor/LL35 lncRNA Contributes to Glucose and Lipid Metabolism In Vitro and In Vivo
Biomedicines
long non-coding RNA
lipid metabolism
glucose metabolism
hepatocyte
liver
title Murine Falcor/LL35 lncRNA Contributes to Glucose and Lipid Metabolism In Vitro and In Vivo
title_full Murine Falcor/LL35 lncRNA Contributes to Glucose and Lipid Metabolism In Vitro and In Vivo
title_fullStr Murine Falcor/LL35 lncRNA Contributes to Glucose and Lipid Metabolism In Vitro and In Vivo
title_full_unstemmed Murine Falcor/LL35 lncRNA Contributes to Glucose and Lipid Metabolism In Vitro and In Vivo
title_short Murine Falcor/LL35 lncRNA Contributes to Glucose and Lipid Metabolism In Vitro and In Vivo
title_sort murine falcor ll35 lncrna contributes to glucose and lipid metabolism in vitro and in vivo
topic long non-coding RNA
lipid metabolism
glucose metabolism
hepatocyte
liver
url https://www.mdpi.com/2227-9059/10/6/1397
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