Upregulation of long noncoding RNAs and is associated with intrahepatic cholangiocarcinoma.

Olga Y Burenina, Natalia L Lazarevich, Inna F Kustova, Daria A Shavochkina, Ekaterina A Moroz, Nikolay E Kudashkin, Yuriy I Patyutko, Maria P Rubtsova, Olga A Dontsova
Author Information
  1. Olga Y Burenina: Center of Molecular and Cellular Biology, Moscow, Russia. ORCID
  2. Natalia L Lazarevich: Biology Department, Lomonosov Moscow State University, Moscow, Russia.
  3. Inna F Kustova: Institute of Carcinogenesis, Blokhin National Medical Research Center of Oncology (affiliated with Russian Ministry of Health), Moscow, Russia.
  4. Daria A Shavochkina: Institute of Carcinogenesis, Blokhin National Medical Research Center of Oncology (affiliated with Russian Ministry of Health), Moscow, Russia.
  5. Ekaterina A Moroz: Institute of Clinical Oncology, Blokhin National Medical Research Center of Oncology (affiliated with Russian Ministry of Health), Moscow, Russia.
  6. Nikolay E Kudashkin: Institute of Clinical Oncology, Blokhin National Medical Research Center of Oncology (affiliated with Russian Ministry of Health), Moscow, Russia.
  7. Yuriy I Patyutko: Institute of Clinical Oncology, Blokhin National Medical Research Center of Oncology (affiliated with Russian Ministry of Health), Moscow, Russia.
  8. Maria P Rubtsova: Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow, Russia.
  9. Olga A Dontsova: Center of Molecular and Cellular Biology, Moscow, Russia.

Abstract

ObjectiveMany long noncoding RNAs (lncRNAs) are associated with liver cancers, mainly hepatocellular carcinoma (HCC) and to a smaller extent intrahepatic cholangiocarcinoma (CCA). Most of such lncRNAs show similar dysregulation patterns when the two types of tumors are compared, suggesting that these aberrations are characteristic features of these liver tumor types. In the present study, we aimed to identify some candidate lncRNAs that are associated specifically with CCA.MethodsAccording to The Cancer Genome Atlas data, we chose , , and as promising biomarkers dysregulated in CCA but unaffected in HCC. We first verified their upregulation in an existing transcriptomic dataset for CCA patients. Next, we estimated expression levels of these three lncRNAs by reverse-transcription quantitative PCR in a group of paired (tumorous/adjacent) postsurgery tissue samples from 110 patients with various liver lesions: CCA, HCC, combined HCC-CCA, or benign liver tumors.ResultsSignificant upregulation of and was noted in most of the investigated CCA samples, whereas in HCC samples, increased expression of these two lncRNAs was observed only in some types of cases (mainly characterized by an advanced tumor stage). In contrast, manifested extremely low expression and no diagnostic potential in all the tested liver samples. Analyzing expression correlations of lncRNAs with candidate genes, we obtained strong evidence for -mediated upregulation of in CCA.ConclusionsFor the first time, we show the upregulation of and in CCA and report their good potential as diagnostic biomarkers for this type of liver tumor.

Keywords

References

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MeSH Term

Humans
Cholangiocarcinoma
RNA, Long Noncoding
Up-Regulation
Bile Duct Neoplasms
Gene Expression Regulation, Neoplastic
Liver Neoplasms
Carcinoma, Hepatocellular
Male
Biomarkers, Tumor
Female
Middle Aged
Serine Proteases

Chemicals

RNA, Long Noncoding
Biomarkers, Tumor
ABHD11 protein, human
Serine Proteases

Word Cloud

Created with Highcharts 10.0.0CCAliverlncRNAsHCCupregulationexpressionsamplesnoncodingassociatedcholangiocarcinomatypestumorlongRNAsmainlyhepatocellularcarcinomaintrahepaticshowtwotumorscandidatebiomarkersfirstpatientsdiagnosticpotentialObjectiveManycancerssmallerextentsimilardysregulationpatternscomparedsuggestingaberrationscharacteristicfeaturespresentstudyaimedidentifyspecificallyMethodsAccordingCancerGenomeAtlasdatachosepromisingdysregulatedunaffectedverifiedexistingtranscriptomicdatasetNextestimatedlevelsthreereverse-transcriptionquantitativePCRgrouppairedtumorous/adjacentpostsurgerytissue110variouslesions:combinedHCC-CCAbenignResultsSignificantnotedinvestigatedwhereasincreasedobservedcasescharacterizedadvancedstagecontrastmanifestedextremelylowtestedAnalyzingcorrelationsgenesobtainedstrongevidence-mediatedConclusionsFortimereportgoodtypeUpregulationLongRNAbiomarkercancer

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