A new research paper was published in Oncotarget, titled “Deconstructing the role of MALAT1 in MAPK-signaling in melanoma: insights from antisense oligonucleotide treatment.”n
The long non-coding RNA (lncRNA) MALAT1 is a regulator of oncogenesis and 31 Mayprotein expression in the MAPK pathway. However, the role of MALAT1 in regulation of gene and protein expression of the MAPK-pathway kinases RAS, RAF, MEK, and ERK in melanoma is largely unknown.n
In this study, researchers Valentin Feichtenschlager, Yixuan James Zheng, Wilson Ho, Linan Chen, Ciara Callanan, Christopher Chen, Albert Lee, Jose Ortiz, Klemens Rappersberger, and Susana Ortiz-Urda from the University of California San Francisco and Medical University Vienna demonstrated the impacts of antisense oligonucleotide (ASO)-based MALAT1-inhibition on MAPK-pathway gene regulation in melanoma.n
“Our results showed that MALAT1-ASO treatment decreased BRAF RNA expression and protein levels, and MALAT1 had increased correlation with MAPK-pathway associated genes in melanoma patient samples compared to healthy skin,” write the researchers.
Additionally, drug-induced MAPK inhibition upregulated MALAT1-expression, a finding that resonates with a paradigm of MALAT1-expression presented in this work: MALAT1 is downregulated in melanoma and other cancer types in which MALAT1 seems to be associated with MAPK-signaling, while MALAT1-ASO treatment strongly reduced the growth of melanoma cell lines, even in cases of resistance to MEK inhibition. MALAT1-ASO treatment significantly inhibited colony formation in vitro and reduced 31 Maymelanoma xenograft mouse model in vivo, while showing no aberrant toxic side effects.n
“Our findings demonstrate new insights into MALAT1-mediated MAPK-pathway gene regulation and a paradigm of MALAT1 expression in MAPK-signaling-dependent cancer types. MALAT1 maintains essential oncogenic functions, despite being downregulated,” conclude the authors.
n Valentin Feichtenschlager et al, Deconstructing the role of MALAT1 in MAPK-signaling in melanoma: insights from antisense oligonucleotide treatment, Oncotarget (2023). 31 MayDOI: 10.18632/oncotarget.28447
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