CRISPR-inhibition screen for lncRNAs linked to melanoma growth and metastasis

作者：Stavroula Petroulia, Kathryn Hockemeyer, Shashank Tiwari, Pietro Berico, Sama Shamloo, Seyedeh Elnaz Banijamali, Eleazar Vega‐Saenz de Miera, Yixiao Gong, Palaniraja Thandapani, Eric Wang, Michael Schulz, Aristotelis Tsirigos, Iman Osman, Ioannis Aifantis, Jochen Imig · 发表于：bioRxiv (Cold Spring Harbor Laboratory) · 年份：2024 · DOI：10.1101/2024.07.24.604899 · 被引用次数：2 · 研究领域：Cancer-related molecular mechanisms research、RNA regulation and disease、interferon and immune responses

Melanoma being one of the most common and deadliest skin cancers, has been rising since the past decade. Patients at advanced stages of the disease have very poor prognoses, as opposed to at the earlier stages. Nowadays the standard-of-care of advanced melanoma is resection followed by immune checkpoint inhibition based immunotherapy. However, a substantial proportion of patients either do not respond or develop resistances. This underscores a need for novel approaches and therapeutic targets as well as a better understanding of the mechanisms of melanoma pathogenesis. Long non-coding RNAs (lncRNAs) comprise a poorly characterized class of functional players and promising targets in promoting malignancy. Certain lncRNAs have been identified to play integral roles in melanoma progression and drug resistances, however systematic screens to uncover novel functional lncRNAs are scarce. Here, we profile differentially expressed lncRNAs in patient derived short-term metastatic cultures and BRAF-MEK-inhibition resistant cells. We conduct a focused growth-related CRISPR-inhibition screen of overexpressed lncRNAs, validate and functionally characterize lncRNA hits with respect to cellular growth, invasive capacities and apoptosis in vitro as well as the transcriptomic impact of our lead candidate the novel lncRNA XLOC_030781. In sum, we extend the current knowledge of ncRNAs and their potential relevance on melanoma. Significance: Previously considered as transcriptional noise, lncRNA...