LncRNA SChLAP1 promotes cancer cell proliferation and invasion via its distinct structural domains and conserved regions.

Abstract

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.