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Does Novel Protein Drive Disease Progression in Multiple Myeloma?

By: Kayci Reyer
Posted: Friday, May 13, 2022

According to research presented in the Journal of Experimental & Clinical Cancer Research, a novel protein known as circHRNPU_603aa may be a driver of disease progression in some patients with multiple myeloma. This protein, encoded by circHNRNPU, appears to interfere with multiple types of cells in the bone marrow microenvironment.

“Overexpressed circHNRNPU_603aa promoted [multiple myeloma] cell proliferation in vitro and in vivo; in contrast, knockdown of circHNRNPU_603aa by [small interfering RNA] abrogated these effects,” noted Chunyan Gu, PhD, of Nanjing University of Chinese Medicine, and colleagues.

The study used SBC-ceRNA microarray chips to evaluate five immunoglobulin D (IgD) multiple myeloma samples, five IgG multiple myeloma samples, and three normal plasma cell samples. In comparison with IgG and normal cell samples, IgD samples had the highest relative presence and differential expression of circHNRNPU within its circular RNA. Across four independent patient groups, an association was noted between higher circHNRNPU expression and poorer outcomes. CircHNRNPU was found to be secreted by multiple myeloma cells; in turn, circHNRNPU encoded the circHNRNPU_603aa protein, which contributed to cancer cell proliferation. CircHNRNPU_603aa was also noted to stabilize c-Myc via SKP2 exon skipping regulation. According to the investigators, this may be associated with the protein’s RGG-box region, which facilitates RNA binding.

Samples underwent Sanger sequencing, RNase R digestion, and quantitative polymerase chain reaction assays to determine the presence and abundance of circHNRNPU, whereas BaseScope RNA ISH assay evaluated the expression of circHNRNPU in paraffin-embedded tissue. In vitro and in vivo testings were performed to better understand the function of circHNRNPU_603aa.

Disclosure: The study authors reported no conflicts of interest.

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