The long noncoding RNA (lncRNA) FAM157C may promote clonal proliferation in patients with paroxysmal nocturnal hemoglobinuria (PNH), according to a recent study published in the Annals of Hematology.

The study authors recruited 35 patients with PNH at the hematology department of Tianjin Medical University General Hospital in China from November 2017 to August 2019 and analyzed CD59 and CD59+ granulocytes from their blood. They performed high-throughput sequencing on 5 of the patients to identify differentially expressed lncRNAs and messenger RNAs (mRNAs) and confirmed these results in the other 30 patients.

In addition, the researchers selected mRNAs with fragments per kilobase of exon model per million mapped fragments (FPKM) of more than 10 in at least 3 patients and performed experiments to identify their upstream regulatory lncRNAs.

They used quantitative reverse transcription polymerase chain reaction (qRT-PCR) to confirm the expression of selected mRNAs and lncRNAs and correlated these expression patterns with clinical data obtained from the remaining participants.

Read more about PNH etiology

Next, the researchers studied the functions of the lncRNAs in the PIGA-KO-THP-1 cell line. They discovered 742 upregulated and 1376 downregulated lncRNAs and 3276 upregulated and 213 downregulated mRNAs. There were 8 highly expressed mRNAs that appeared to be related to the NF-κB pathway, and their coexpression patterns were also studied.

According to the results, LINC01002, FAM157C, CTD-2530H12.2, XLOC-064331, and XLOC-106677 were correlated with the 8 mRNAs. The lncRNA FAM157C was found to be upregulated in the PNH clone, and its expression was positively correlated with lactate dehydrogenase levels and CD59 granulated and monocyte cell ratios.

After the knockdown of the FAM157C gene in the PIGA-KO-THP-1 cell line, the researchers also found arrested cells in the G0/G1 and S phases, increased apoptosis rates, and reduced cell proliferation.

“This is the first study to explore the role of lncRNAs in PNH. Fully understanding the role of lncRNAs involved in the pathogenesis of PNH may provide more new and accurate strategies in treatment,” Wang and colleagues wrote.

LncRNAs hold a variety of biological functions, including the regulation of gene expression, cell differentiation, and proliferation, but their role in PNH remains unclear.

Reference

Wang H, Liu H, Li L, et al. Long noncoding RNA FAM157C contributes to clonal proliferation in paroxysmal nocturnal hemoglobinuria. Ann Hematol. Published online January 6, 2023. doi:10.1007/s00277-022-05055-8