Polymorphisms in KSHV-encoded microRNA sequences affect levels of mature viral microRNA in Kaposi Sarcoma lesions

The cover for issue 88 of Oncotarget features Figure 5, "Comparison between mature KSHV microRNA expression in KS tumor biopsies from HAMB and from UW," by Marshall, et al.

The research team demonstrated that micro RNAs with variant sequence have different maturation and mature micro RNA expression in vitro. They also illustrate the association between micro RNA sequence and changes in mature micro RNA levels within Kaposi sarcoma lesions. Levels of mature KSHV micro RNAs were measured with 21 custom small RNA qRT-PCR assays using RNA RNU6B as endogenous control.

Dr. Denise Whitby from the AIDS and Cancer Virus Program, at the Frederick National Laboratory for Cancer Research, in Frederick, MD, USA said, "Kaposis sarcoma-associated herpesvirus is the causative agent of two B-cell lymphoproliferative diseases, primary effusion lymphoma and a variant of multicentric Castlemans disease, as well as Kaposis sarcoma."

The discovery of KSHV-encoded micro RNAs offered the opportunity to examine sequence variations in a coding region of KSHV with the potential to affect viral and host gene expression patterns. Phylogenetic analysis showed micro RNA sequences clustered into an A/C branch, including sequences derived from patients in North America and Europe; and a B/F branch, consisting predominantly of sequences identified in KSHV infecting African individuals and MCD patients.

Figure 5: Comparison between mature KSHV microRNA expression in KS tumor biopsies from HAMB and from UW. Log transformed levels, normalized to the host transcript RNU6B and to control samples are shown. Statistically significantly elevated microRNA expression was noted in K12-5-3p and K12-5-5p in samples from South Africa compared to the U.S., while K12-9-5p was decreased.

In addition, the researchers demonstrated that SNPs in some pre-micro RNA sequences affected micro RNA processing and mature micro RNA production in a complex manner in vitro.

In the current study, they examined micro RNA sequence variation in KS patients in the US and South Africa and assessed mature KSHV micro RNAs levels within KS lesions to investigate potential correlations.

Furthermore, to explore whether such correlations were associated with the cumulative effects of SNPs on secondary structure, they derived in silico the RNA structure of both a representative US and variant South African KSHV micro RNA cluster sequence.

The Denise Whitby research team concluded, "although the structural characteristics and sequence elements required for micro RNA processing are incompletely defined, our data, in the context of the current literature, suggest that micro RNA processing can be profoundly altered by SNPs in the pri-, pre-, and mature micro RNA sequences."

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DOI - https://doi.org/10.18632/oncotarget.26321

Full text - https://www.oncotarget.com/article/26321/text/

Correspondence to - Denise Whitby - whitbyd@mail.nih.gov

Keywords - KSHV, microRNA, Kaposi's sarcoma