Key circular RNAs identified in male osteoporosis patients by whole transcriptome sequencing

Haijin Zhang1, Xue Song2, Zongyan Teng1

  • 1Department of Geriatrics, The Second Affiliated Hospital of Harbin Medical University, Harbin, China.

Peerj
|June 14, 2021
PubMed
Abstract

Insights

Circular RNAs (circRNAs) are implicated in male osteoporosis. This study identified key circRNAs in osteoporosis patients, suggesting their potential as diagnostic and therapeutic targets.

Area of Science:

  • Genomics
  • Molecular Biology
  • Biochemistry

Background:

  • Osteoporosis (OP) is a systemic bone disease characterized by bone loss and microstructural deterioration.
  • Noncoding RNAs (ncRNAs), particularly circular RNAs (circRNAs), are increasingly recognized for their roles in various diseases.
  • The specific role and expression of circRNAs in male osteoporosis remain largely unexplored.

Purpose of the Study:

  • To investigate the expression profile of circular RNAs (circRNAs), messenger RNAs (mRNAs), and microRNAs (miRNAs) in male osteoporosis.
  • To elucidate the underlying mechanisms of circRNAs in the pathogenesis of male osteoporosis.
  • To identify potential circRNA biomarkers for osteoporosis diagnosis and treatment.

Main Methods:

  • Whole transcriptome sequencing was performed on peripheral blood samples from male osteoporosis patients and healthy controls (≥60 years old).
  • Differential expression analysis was conducted for mRNAs, circRNAs, and miRNAs.
  • Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genes (KEGG) pathway enrichment analyses were performed.
  • A circRNA-miRNA-mRNA regulatory network was constructed.
  • Key circRNAs were identified and validated using quantitative polymerase chain reaction (qPCR).

Main Results:

  • A total of 398 circRNAs, 51 miRNAs, and 642 mRNAs were found to be significantly differentially expressed in osteoporosis patients compared to controls.
  • Enrichment analysis revealed that host genes of differentially expressed circRNAs are primarily involved in cell cycle regulation, organelle components, protein binding, and signaling pathways (e.g., Toll-like receptor, TNF, thyroid hormone).
  • A regulatory network highlighted key circRNAs, with hsa_circ_0042409 identified and validated as a significant circRNA in osteoporosis.

Conclusions:

  • Circular RNAs play a significant role in the pathogenesis of osteoporosis.
  • Identified key circRNAs, such as hsa_circ_0042409, represent potential biomarkers for osteoporosis diagnosis.
  • These circRNAs may serve as novel therapeutic targets for managing osteoporosis.

Related Concept Videos

Ribosome Profiling02:24

Ribosome Profiling

Ribosome profiling or ribo-sequencing is a deep sequencing technique that produces a snapshot of active translation in a cell. It selectively sequences the mRNAs protected by ribosomes to get an insight into a cell’s translation landscape at any given point in time.
Applications of ribosome profiling
Ribosome profiling has many applications, including in vivo monitoring of translation inside a particular organ or tissue type and quantifying new protein synthesis levels.
The technique...
3.8K
The Nucleolus02:55

The Nucleolus

The nucleolus is the most prominent substructure of the nucleus. When it was first discovered, it was considered to be an isolated organelle that forms fibrils and granules. In 1931, the relationship between the nucleolus and chromosomes was first described by Heitz. He observed that the appearance and size of nucleolus varies depending on the stage of the cell cycle. He also noticed constricted regions on different chromosomes clustered together at definite cell cycle stages. These regions,...
9.6K
Leaky Scanning02:28

Leaky Scanning

During most eukaryotic translation processes, the small 40S ribosome subunit scans an mRNA from its 5' end until it encounters the first start AUG codon. The large 60S ribosomal subunit then joins the smaller one to initiate protein synthesis. The location of the translation initiation is largely determined by the nucleotides near the start codon as there may be multiple translation initiation sites present on the mRNA.  Marilyn Kozak discovered that the sequence RCCAUGG (where R...
5.3K