Expression profiling of microRNAs and isomiRs in conventional central chondrosarcoma

Abstract

Conventional central chondrosarcoma (CCC) is a malignant bone tumor that is characterized by the production of chondroid tissue. Since radiation therapy and chemotherapy have limited effects on CCC, treatment of most patients depends on surgical resection. This study aimed to identify the expression profiles of microRNAs (miRNAs) and isomiRs in CCC tissues to highlight their possible participation to the regulation of pathways critical for the formation and growth of this type of tumor. Our study analyzed miRNAs and isomiRs from Grade I (GI), Grade II (GII), and Grade III (GIII) histologically validated CCC tissue samples. While the different histological grades shared a similar expression profile for the top abundant miRNAs, we found several microRNAs and isomiRs showing a strong different modulation in GII + GIII vs GI grade samples and their involvement in tumor biology could be consistently hypothesized. We then in silico validated these differently expressed miRNAs in a larger chondrosarcoma public dataset and confirmed the expression trend for 17 out of 34 miRNAs. Our results clearly suggests that the contribution of miRNA deregulation, and their targeted pathways, to the progression of CCC could be relevant and strongly indicates that when studying miRNA deregulation in tumors, not only the canonical miRNAs, but the whole set of corresponding isomiRs should be taken in account. Improving understanding of the precise roles of miRNAs and isomiRs over the course of central chondrosarcoma progression could help identifying possible targets for precision medicine therapeutic intervention.

Emerging Role of isomiRs in Cancer: State of the Art and Recent Advances

“…Parafioriti et al [ 139 ] performed miRNoma profiling in chondrosarcoma tissues and identified several differentially expressed miRNAs and isomiRs in grade II-III compared with grade I samples. Analyzing predicted target genes, particularly for 5′ end isoforms, the authors observed that many of the pathways targeted by these isomiRs were involved in cancer-associated signaling, also suggesting a synergistic role with the canonical counterparts.…”

isomiRs–Hidden Soldiers in the miRNA Regulatory Army, and How to Find Them?

“…IsomiRs have been associated with several human diseases such as pre-eclampsia [ 106 ], Huntington disease [ 107 ], Alzheimer’s disease [ 108 ], osteoarthritis [ 109 ], cardiovascular diseases [ 110 ], rheumatoid arthritis [ 111 ], and found to respond to bacterial infection [ 112 ]. Specific isomiR expression patterns have been observed in various cancer types [ 113 , 114 ] suggesting the miRNA-mediated level of regulation of tumorigenesis. In gastric cancer, several mature miRNAs generated from the two different arms (5p or 3p) of the same pre-miRNA exhibit reversed expression preferences (normal vs. cancer tissue) [ 115 ].…”

“…Furthermore, the combination of isomiR features with state-of-the-art algorithms effectively differentiated normal from cancer cell lines [ 118 , 122 ]. Mature miRNAs and their isomiR variants, along with their target pathways, should be considered during tumor diagnosis, progression and treatment monitoring [ 114 ].…”

Tumor IsomiR Encyclopedia (TIE): a pan-cancer database of miRNA isoforms

“…Interestingly, it has been shown that alteration in isomiR profiles (rather than overall miRNA abundance) correlates with cancer progression, which suggests a unique role for isomiRs in tumorigenesis [22,23] . Multiple reports suggest that isomiRs can be used as biomarkers for tumor detection, classification and patients prognosis [24][25][26][27] . These observations highlight the importance of having computational tools to analyze isomiR expression profiles from sequencing data to further investigate their functions.…”