Alternative splicing of RNA is an essential mechanism that increases proteomic diversity in eukaryotic cells. Aberrant alternative splicing is often associated with various human diseases, including cancer. We conducted whole-transcriptome analysis of 18 osteosarcoma bone samples (paired normal—tumor biopsies). Using RNA-seq, we identified statistically significant (FDR <0.05) 26 differentially expressed transcript variants of leptin receptor overlapping transcript (LEPROT) gene. Some of the transcripts were overexpressed in normal cells, whereas others were overexpressed in tumor cells. The function of LEPROT is not completely understood. Herein, we highlight a possible association between OS and aberrant alternative splicing events and its interaction with the expression of LEPROT. We also discuss the role of LEPROT in regulating growth hormone and its receptor, and the relationship with initiation and progression of OS. This research study may help to understand the association of alternative splicing mechanism in OS and in tumorigenesis more generally. Further, LEPROT gene can also be considered as a potential biomarker of osteosarcoma.

Impact statement

Osteosarcoma (OS, also known as osteogenic sarcoma) is the most common primary malignancy of bone in children and adolescents. The molecular mechanisms of OS are extremely complicated and its molecular mediators remain to be elucidated. We sequenced total RNA from 18 OS bone samples (paired normal—tumor biopsies). We found statistically significant (FDR <0.05) 26 differentially expressed transcript variants of LEPROT gene with different expressions in normal and tumor samples. These findings contribute to the understanding of molecular mechanisms of OS development and provide encouragement to pursue further research.

中文翻译：

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骨肉瘤中瘦素受体重叠转录物的可变剪接

RNA的可变剪接是增加真核细胞蛋白质组学多样性的重要机制。异常的可变剪接通常与各种人类疾病有关，包括癌症。我们对18个骨肉瘤骨样品（配对的正常肿瘤活检）进行了全转录组分析。使用RNA序列，我们确定了瘦素受体重叠转录（LEPROT）基因的统计学差异显着（FDR <0.05）26差异表达的转录变体。一些转录本在正常细胞中过表达，而另一些在肿瘤细胞中过表达。LEPROT的功能尚不完全清楚。在这里，我们重点介绍OS与异常替代剪接事件之间的可能关联，以及其与LEPROT。我们还讨论了LEPROT在调节生长激素及其受体中的作用，以及与OS的发生和发展的关系。这项研究可能有助于了解OS和肿瘤发生过程中可变剪接机制的关联。此外，LEPROT基因也可以被认为是骨肉瘤的潜在生物标志物。

影响陈述

骨肉瘤（OS，也称为成骨​​肉瘤）是儿童和青少年中最常见的原发性骨恶性肿瘤。OS的分子机制极其复杂，其分子介体仍有待阐明。我们对18个OS骨样品（配对的正常肿瘤活检）中的总RNA进行了测序。我们发现具有统计学意义（FDR <0.05）的26个差异表达的LEPROT基因转录变异体在正常和肿瘤样品中具有不同的表达。这些发现有助于理解OS发育的分子机制，并为进一步研究提供了鼓励。