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Team Profiles Differentially Expressed MicroRNAs in Penile Cancer

NEW YORK (GenomeWeb) – In a study appearing online yesterday in PLOS One, Chinese researchers reported that they have tracked down dozens of microRNAs that appear to be differentially expressed in penile cancer tumors.

The team identified hundreds of known miRNAs in its RNA sequencing analyses of matched tumor and normal samples from 10 men with penile cancer. Comparisons between each tumor-normal pair — coupled with quantitative real-time PCR validation on a subset of miRNAs — pointed to 56 miRNAs with higher- or lower-than-usual levels in the penile tumors.

The apparently misregulated miRNAs roughly overlapped with those described in studies of prostate, testis, bladder, and other genitourinary cancers, the researchers noted. In particular, the penile cancers tended to involve miRNA alterations expected to shift the regulation of genes in pathways related to cell proliferation, genomic stability, cell connections, and other processes believed to boost cancer development and advancement.

Consequently, the study's authors argued that their miRNA findings "provide a valuable research resource to further elucidate the regulatory roles of miRNAs in penile tumorigenesis and progression," and may facilitate the development of novel diagnostic biomarkers and effective therapeutic strategies for penile cancer.

Perhaps due to their rarity, penile cancers remain poorly characterized molecularly, the researchers noted, and show disproportionately high rates of mortality and morbidity. The disease has been linked to glitches in pathways containing TP53, CDKN2A, and a few other genes, though environmental factors such as smoking, human papillomavirus infection, and chronic inflammation have also been implicated in penile cancer risk.

"[W]e aimed at filling the gap in information regarding the miRNA profile in human penile cancer," the team explained, "and evaluated a possible correlation between differentiated miRNA expression levels with tumorigenesis and progression."

To that end, the researchers got BGI-Shenzhen to do Illumina HiSeq 2000 sequencing on pooled small RNA libraries from fresh-frozen penile cancer samples and matched normal penile tissue, representing 10 men with penile squamous cell carcinoma who were treated at the First Affiliated Hospital of Anhui Medical University between 2013 and 2015.

When the team scrutinized the resulting reads, focusing on small RNAs spanning 18 to 32 nucleotides apiece, it detected 806 miRNAs in the pooled penile cancer sequence data and 751 miRNAs in matched normal reads. It also picked up reads corresponding to hundreds of new miRNA candidates, including predicted Piwi-interacting RNAs, messenger RNAs, ribosomal RNAs, and other small RNA entities.

The researchers initially highlighted almost 100 miRNAs with apparent expression differences in the normal and cancerous tissues, whittling this set of differentially expressed miRNAs down to 56 following quality control steps.

Among the 26 miRNAs with jacked up expression in the tumors and the 30 miRNAs found at lower-than-usual levels in penile cancer, the team saw an over-representation of miRNAs suspected of targeting genes in pathways involved with cell-cell junction formation, cell growth, shape, and proliferation, angiogenesis, apoptosis, kinase signaling, and more.

"Several differentially expressed miRNAs potentially target networks of genes and signaling pathways probably … involved in the malignant transformation of normal penis to [penile cancer]," the study's authors concluded, arguing that the current results should serve as a resource to inform future studies of penile cancer formation, progression, diagnosis, and treatment.