Whole Blood Expression Levels of Long Noncoding RNAs: HOTAIRM1, GAS5, MZF1-AS1, and OIP5-AS1 as Biomarkers in Adolescents with Obesity-Related Asthma

Int J Mol Sci. 2023 Mar 30;24(7):6481. doi: 10.3390/ijms24076481.

Abstract

Asthma is a heterogeneous entity encompassing distinct endotypes and varying phenotypes, characterized by common clinical manifestations, such as shortness of breath, wheezing, and variable airflow obstruction. Two major asthma endotypes based on molecular patterns are described: type 2 endotype (allergic-asthma) and T2 low endotype (obesity-related asthma). Long noncoding RNAs (lncRNAs) are transcripts of more than 200 nucleotides in length, currently involved in many diverse biological functions, such as chromatin remodeling, gene transcription, protein transport, and microRNA processing. Despite the efforts to accurately classify and discriminate all the asthma endotypes and phenotypes, if long noncoding RNAs could play a role as biomarkers in allergic asthmatic and adolescent obesity-related asthma, adolescents remain unknown. To compare expression levels of lncRNAs: HOTAIRM1, OIP5-AS1, MZF1-AS1, and GAS5 from whole blood of Healthy Adolescents (HA), Obese adolescents (O), allergic asthmatic adolescents (AA) and Obesity-related asthma adolescents (OA). We measured and compared expression levels from the whole blood of the groups mentioned above through RT-q-PCR. We found differentially expressed levels of these lncRNAs between the groups of interest. In addition, we found a discriminative value of previously mentioned lncRNAs between studied groups. Finally, we generated an interaction network through bioinformatics. Expression levels of OIP5-AS1, MZF1-AS1, HOTAIRM1, and GAS5 in whole blood from the healthy adolescent population, obese adolescents, allergic asthma adolescents, and obesity-related asthma adolescents are differently expressed. Moreover, these lncRNAs could act as molecular biomarkers that help to discriminate between all studied groups, probably through molecular mechanisms with several genes and miRNAs implicated.

Keywords: HOTAIRM1; MZF1-AS1; OIP5-AS1; asthma; lncRNA GAS5; long noncoding RNAs; obesity-related asthma.

MeSH terms

  • Adolescent
  • Asthma* / genetics
  • Biomarkers
  • Cell Proliferation / genetics
  • Humans
  • Kruppel-Like Transcription Factors
  • MicroRNAs* / genetics
  • MicroRNAs* / metabolism
  • Pediatric Obesity* / complications
  • Pediatric Obesity* / genetics
  • RNA, Long Noncoding* / genetics
  • RNA, Long Noncoding* / metabolism

Substances

  • RNA, Long Noncoding
  • MicroRNAs
  • Biomarkers
  • MZF1 protein, human
  • Kruppel-Like Transcription Factors

Grants and funding

This work was supported by the Mexican government for the Children’s Hospital of Mexico Federico Gómez under grant numbers HIM/2013/015.SSa.1061. Publication costs will be covered by Children’s Hospital of Mexico Federico Gómez.