Multiple myeloma associated long non-coding RNA PLUM confers chemoresistance by enhancing PRC2 mediated UPR pathway activation.

ABSTRACT: Multiple myeloma (MM) is the second most common hematological malignancy that displays diverse genetic heterogeneity leading to treatment resistance. Recurrent mutations causing hyperactivation of the non-canonical NF-ĸB pathway are highly prevalent in relapsed, refractory MM patients, but the precise mechanisms driving chemoresistance are poorly understood. Here, we identify a long non-coding RNA termed PLUM, that is overexpressed in NF-ĸB mutant high-risk MM subtypes and patients who are refractory to VRd treatment regimen. Mechanistically, PLUM interacts with Polycomb Repressive Complex 2 to regulate its stability and histone methyltransferase activity, modulating the expression of tumor suppressor genes, FOXO3 and ZFP36, to activate the unfolded protein response (UPR). Importantly, dis

SUBMITTER: Deka K 

PROVIDER: S-EPMC12402260 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature