Identification and validation of the m6A-binding protein LRPPRC to promote tumorigenesis in multiple myeloma

Abstract

Objectives To explore the clinical relevance and biological roles of the N6-methyladenosine (m6A) binding protein leucine-rich pentatricopeptide repeat-containing protein (LRPPRC) in multiple myeloma (MM), aiming to offer new insights into its potential as a prognostic marker for MM.Methods Bioinformatics methodologies were employed to identify m6A-associated differential expression genes (DEGs) in different kinds of datasets. Quantitative Real-Time PCR (qRT-PCR) were used to analyze DEG LRPPRC in both bone marrow of MM patients and MM cell lines. In vitro experiments, by using LRPPRC knockdown cell line model, CCK-8 assays, cell cycle analyzes, and apoptosis assays, were conducted to assess the biological role of LRPPRC on MM progression.Results Bioinformatics analysis identified LRPPRC as a critical m6A DEG in MM. Over-expression LRPPRC was positively correlated with the staging of MM and associated with poorer prognosis in MM patients. Furthermore, we confirmed elevated LRPPRC expression in three MM cell lines U266, RPMI-8226, and MM.1S as well as in the bone marrow of MM patients by real-time PCR or western blot. Additionally, LRPPRC expression demonstrated a positive correlation with the International Staging System (ISS) stages of MM. Furthermore, LRPPRC knockdown inhibited the proliferation of MM cells by CCk-8 assay, enhanced apoptosis, and cell cycle analysis showed that inhibition of LRPPRC increased the proportion of G1-phase cells and decreased the proportion of G2-phase cells in MM cells.Conclusion LRPPRC promote tumorigenesis in MM and may serve as a potential prognostic target for MM.

Keywords

• LRPPRC
• multiple myeloma
• m6A
• bioinformatics analysis
• prognostic marker