Oh Mihyun, Kadam Roshni Nagesh, Charania Zahra Sadruddin, Somarowthu Srinivas
Graduate Program in Molecular and Cell Biology and Genetics, Graduate School of Biomedical Sciences and Professional Studies, College of Medicine, Drexel University, Philadelphia, PA, USA.
Department of Biochemistry and Molecular Biology, College of Medicine, Drexel University, Philadelphia, PA, USA.
J Mol Biol. 2025 Oct 1;437(19):169350. doi: 10.1016/j.jmb.2025.169350. Epub 2025 Jul 17.
Long non-coding RNAs (lncRNAs) play key roles in a range of biological processes and disease progression. Despite their functional significance and therapeutic potential, lncRNAs' mechanisms of action remain understudied. One such lncRNA is the Second Chromosome Locus Associated with Prostate-1 (SChLAP1). SChLAP1 is overexpressed in malignant prostate cancer and is associated with unfavorable patient outcomes, such as metastasis and increased mortality. In this study, we demonstrated that SChLAP1 possesses distinct structural domains and conserved regions that may contribute to its function. We determined the secondary structure of SChLAP1 using chemical probing methods combined with mutational profiling (DMS-MaP and SHAPE-MaP). Our in vitro secondary structural model revealed that SChLAP1 consists of two distinct secondary structural modules located at its 5' and 3' ends, both featuring regions with a high degree of structural organization. Our in vivo chemical probing identified structurally stable regions and areas that may undergo specific structural rearrangements in the cellular context. Overexpression of the modules led to a notable increase in cancer cell proliferation and invasion, proving their functional significance in the oncogenicity of SChLAP1. In conclusion, we discovered functionally important, independent modules with well-defined structures of SChLAP1. These results will serve as a guide to explore the detailed molecular mechanisms by which SChLAP1 promotes aggressive prostate cancer, ultimately contributing to the development of SChLAP1 as a novel therapeutic target.
长链非编码RNA（lncRNAs）在一系列生物过程和疾病进展中发挥着关键作用。尽管lncRNAs具有功能重要性和治疗潜力，但其作用机制仍未得到充分研究。其中一种lncRNA是与前列腺-1相关的二号染色体位点（SChLAP1）。SChLAP1在恶性前列腺癌中过表达，并与不良的患者预后相关，如转移和死亡率增加。在本研究中，我们证明SChLAP1具有独特的结构域和保守区域，这些可能有助于其功能。我们使用化学探针方法结合突变分析（DMS-MaP和SHAPE-MaP）确定了SChLAP1的二级结构。我们的体外二级结构模型显示，SChLAP1由位于其5'和3'端的两个不同的二级结构模块组成，两者均具有高度结构组织的区域。我们的体内化学探针鉴定了结构稳定区域以及在细胞环境中可能发生特定结构重排的区域。这些模块的过表达导致癌细胞增殖和侵袭显著增加，证明了它们在SChLAP1致癌性中的功能重要性。总之，我们发现了SChLAP1功能重要、结构明确的独立模块。这些结果将为探索SChLAP1促进侵袭性前列腺癌的详细分子机制提供指导，最终有助于将SChLAP1开发为一种新型治疗靶点。
