LncRNA FEZF1‐AS1 accelerates multiple myeloma progression by regulating IGF2BP1/BZW2 signaling

Abstract

Multiple myeloma (MM) is the second largest hematological tumor with clonal proliferation of malignant plasma cells. Growing reports have revealed that the dysregulation of long non‐coding RNA (lncRNA) is involved in the MM progression. Nevertheless, lncRNA FEZF1 antisense RNA 1 (FEZF1‐AS1) remain not deeply explored. The RNA transcripts and protein level of MM‐associated molecule were measured by quantitative real‐time polymerase chain reaction or western blot assays, respectively. The clinical correlation was analyzed by Pearson analysis. Molecular interactions among lncRNA FEZF1‐AS1, basic leucine zipper and W2 domain 2 (BZW2) and insulin‐like growth factor 2 mRNA‐binding protein 1 (IGF2BP1) were verified by RNA immunoprecipitation and RNA pull‐down assays. The survival of MM cells was detected by cell counting kit‐8 and flow cytometry assays. Xenograft tumor in vivo was performed to assess tumor growth. The RNA transcripts of lncRNA FEZF1‐AS1, BZW2 and IGF2BP1 were upregulated in MM samples compared to those in healthy donors. Knockdown of lncRNA FEZF1‐AS1 could inhibit the proliferation and induce cell apoptosis in vitro and in vivo. Besides, lncRNA FEZF1‐AS1 could maintain the stability of BZW2 mRNA by interacting IGF2BP1. Moreover, BZW2 silence also downregulated the proliferation but enhanced apoptosis of MM cells, while BZW2 overexpression had an opposite role, which dramatically reversed the regulatory roles of lncRNA FEZF1‐AS1. Altogether, lncRNA FEZF1‐AS1 facilitated MM development by regulating IGF2BP1/BZW2 signaling, suggesting that lncRNA FEZF1‐AS1 might be a candidate for MM treatment.

The complex nature of lncRNA-mediated chromatin dynamics in multiple myeloma

“…Notably, lncRNAs have the ability to influence the stability and degradation of enzymes involved in m6A, as well as facilitate their integration into protein complexes (85-87). One example of this function is the lncRNA FEZF1-AS1, the knockdown of which led to an increased apoptosis by regulating the signalling of IGF2BP1, an m6A reader protein, in MM (88). Furthermore, dysregulation of m6A-related enzymes has been associated with disease progression, enhancing tumour growth and cell proliferation in MM (89)(90)(91)(92)(93)(94)(95).…”

Novel cuproptosis-related lncRNAs can predict the prognosis of patients with multiple myeloma

“…Furthermore, the expression of lncRNAs usually changes and is related to the prognosis of various cancer patients. Mounting evidence supports the independent prognostic value of lncRNAs in patients with MM, leading to the development of multiple prognostic lncRNA signatures ( 32 , 33 ).…”