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.

传统的中央软骨肉瘤（CCC）是一种恶性骨肿瘤，其特征是产生软骨样组织。由于放疗和化疗对 CCC 的疗效有限，大多数患者的治疗依赖于手术切除。本研究旨在鉴定 CCC 组织中 microRNA (miRNA) 和 isomiR 的表达谱，以强调它们可能参与调节此类肿瘤形成和生长的关键途径。我们的研究分析了来自 I 级 (GI)、II 级 (GII) 和 III 级 (GIII) 组织学验证的 CCC 组织样本的 miRNA 和 isomiR。虽然不同组织学级别的最高丰度 miRNA 具有相似的表达谱，但我们发现几种 microRNA 和 isomiR 在 GII + GIII 与 GI 级别样本中表现出强烈不同的调节，并且可以一致地假设它们参与肿瘤生物学。然后，我们在更大的软骨肉瘤公共数据集中通过计算机验证了这些不同表达的 miRNA，并确认了 34 个 miRNA 中 17 个的表达趋势。我们的结果清楚地表明，miRNA 失调及其靶向途径对 CCC 进展的贡献可能是相关的，并且强烈表明，在研究肿瘤中 miRNA 失调时，不仅应该考虑典型的 miRNA，还应该考虑整套相应的 isomiR。考虑在内。加深对 miRNA 和 isomiR 在中央软骨肉瘤进展过程中的精确作用的了解，有助于确定精准医学治疗干预的可能靶点。