Identification and validation of the m6A-binding protein LRPPRC to promote tumorigenesis in multiple myeloma
Jiaxin Tang1, Jing Li1, Shiyu Qin1
1Department of Clinical Laboratory, The Affiliated Hospital of Qingdao University, Qingdao.
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.
Insights
Leucine-rich pentatricopeptide repeat-containing protein (LRPPRC) is elevated in multiple myeloma (MM) and linked to worse outcomes. Inhibiting LRPPRC reduces MM cell growth and promotes apoptosis, suggesting it as a potential prognostic marker.
Area of Science:
- Oncology
- Molecular Biology
- Epigenetics
Background:
- Multiple myeloma (MM) is a hematological malignancy with complex molecular underpinnings.
- N6-methyladenosine (m6A) modification is increasingly recognized for its role in cancer development.
- Leucine-rich pentatricopeptide repeat-containing protein (LRPPRC) is an m6A-binding protein with largely unexplored roles in MM.
Purpose of the Study:
- To investigate the clinical significance and biological functions of LRPPRC in multiple myeloma.
- To evaluate LRPPRC as a potential prognostic biomarker for MM patients.
Main Methods:
- Bioinformatics analysis to identify m6A-associated differential expression genes (DEGs) in MM datasets.
- Quantitative Real-Time PCR (qRT-PCR) and Western blot to assess LRPPRC expression in patient samples and cell lines.
- In vitro experiments including LRPPRC knockdown, CCK-8 assays, cell cycle, and apoptosis analyses to determine LRPPRC's biological role.
Main Results:
- LRPPRC was identified as a critical m6A-associated DEG in MM, with its overexpression correlating positively with MM staging and poorer prognosis.
- Elevated LRPPRC expression was confirmed in MM patient bone marrow and MM cell lines.
- LRPPRC knockdown significantly inhibited MM cell proliferation, induced apoptosis, and altered cell cycle distribution (increased G1, decreased G2 phase).
Conclusions:
- LRPPRC promotes tumorigenesis in multiple myeloma.
- LRPPRC represents a potential therapeutic target and prognostic marker for MM.
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