Characterization of novel small non-coding RNAs and their modifications in bladder cancer using an updated small
Zhangli Su1,2, Ida Monshaugen3,4,5, Arne Klungland3,6
1Department of Genetics, University of Alabama at Birmingham, Birmingham, AL, United States.
Frontiers in Molecular Biosciences
|August 4, 2022
Summary
Non-microRNA small RNAs, including tRNA and ribosomal RNA fragments, are abundant in bladder cancer (BLCA) and show modifications. These small RNAs and their modifications are promising biomarkers for BLCA detection and follow-up.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Bladder cancer (BLCA) is a prevalent malignancy with significant mortality, necessitating improved diagnostic and therapeutic strategies.
- Small non-coding RNAs, particularly microRNAs, are implicated in cancer, but other small RNA families' roles in BLCA remain underexplored.
- Elevated levels of free modified nucleosides in urine suggest small RNAs and their modifications may serve as BLCA biomarkers.
Purpose of the Study:
- To perform a genome-wide analysis of small RNAs (<40 nucleotides) and their modification status in BLCA.
- To identify novel small RNA molecules and potential biomarkers for BLCA detection and management.
Main Methods:
- Small RNA profiling (<40 bases) was conducted on 12 non-muscle invasive papillary urothelial carcinoma (BLCA) tumor specimens.
- A modified protocol using thermostable group II reverse transcriptase (TGIRT) was employed for enhanced small RNA identification and modification analysis.
- Analysis focused on identifying non-microRNA small RNAs and detecting potential base modifications via mismatch sites.
Main Results:
- A significant portion (57 ± 15%) of sequencing reads mapped to non-microRNA small RNAs, including tRNA-derived fragments (tRFs), ribosomal RNA-derived fragments (rRFs), and YRNA-derived fragments (YRFs).
- Potential base modifications, such as N1-methyladenosine (m1A), N1-methylguanosine (m1G), and N2,N2-dimethylguanosine (m22G), were identified on tRFs.
- Mismatch sites on rRFs corresponded to known modifications on 28S and 18S ribosomal RNA.
Conclusions:
- Non-microRNA small RNAs, particularly tRFs and rRFs, are abundant in BLCA tumor tissues.
- TGIRT sequencing can capture small RNA modifications as mismatch sites, indicating potential biological relevance.
- Both non-microRNA small RNAs and their modifications warrant further investigation as potential biomarkers for BLCA diagnosis and monitoring.
