In an innovative study published in the journal Acta Academiae Medicinae Sinicae, researchers have revealed the pivotal role of ribosomal protein S9 (RPS9) in the pathogenesis of multiple myeloma (MM), offering fresh insights into potential therapeutic targets for this debilitating condition. The comprehensive study not only delves into RPS9’s influence on the survival and proliferation of myeloma cells but also provides a foundation for future investigations aimed at improving the prognostic outcomes for MM patients.
Multiple myeloma represents a complex hematological malignancy characterized by the proliferation of plasma cells in the bone marrow. Despite numerous advancements in MM treatment, long-term survival remains challenging, necessitating ongoing research into novel therapeutic targets and biomarkers. Against this backdrop, researchers Song Kun et al. embarked on a mission to uncover the expression and functional significance of RPS9 in myeloma cells.
The research team, hailing from the Beilun People’s Hospital and Zhejiang University First Affiliated Hospital Beilun Branch, employed quantitative polymerase chain reaction (qPCR) and Western blot analysis to evaluate RPS9 expression in bone marrow mononuclear cells from healthy volunteers and CD138+ cells extracted from bone marrow samples of MM patients. Their findings were striking, revealing a significantly higher RPS9 expression in MM patients compared to the control group. Additionally, higher RPS9 levels were associated with extramedullary invasion and a lower overall survival rate, indicating the protein’s potential as a prognostic marker.
To further explore RPS9’s role in MM, the researchers engineered RPMI 8226 myeloma cells with RPS9 knockdown vector and investigated the subsequent biological changes. The knockdown of RPS9 expression led to increased apoptosis and a reduction in cell proliferation and G2 phase cells’ proportion, indicating a halting impact on myeloma cell growth and survival.
The significance of RPS9 extends beyond mere expression levels; its interaction with key molecular pathways further underscores its biological relevance in MM. Specifically, the study highlights the relationship between RPS9 and the nuclear factor-kappa B (NF-κB) signaling pathway, which plays a crucial role in inflammation, immune response, and cancer progression. They discovered that RPS9 positively correlates with sentrin-specific protease 1 (SENP1), an entity instrumental in the post-translational modification processes involved in regulating the NF-κB pathway.
Knocking down RPS9 inhibited SENP1 expression and subsequently impeded the phosphorylation of NF-κB subunit P65 and inhibitor IκBα. These findings indicate a scenario where reduced RPS9 expression can blunt NF-κB pathway activation, a critical component in MM pathophysiology. Meanwhile, overexpression of SENP1 appeared to undermine these effects and even mitigated RPS9-induced apoptosis, underlining a complex interplay between RPS9, SENP1, and NF-κB in MM.
This groundbreaking research, DOI: 10.3881/j.issn.1000-503X.10872, showcases the multifaceted influence of RPS9 on MM cell biology, from apoptosis and cell cycle regulation to signaling pathways. The implications for targeted therapy are substantial; modulating RPS9 expression or function could halt MM progression or enhance the effectiveness of existing treatments.
References
1. Song, K., Peng, S., Za, J. L., Wang, B., & Chen, B. (2019). Ribosomal Protein S9 Expression in Multiple Myeloma and Its Effect on Cell Biological Function. Acta Academiae Medicinae Sinicae, 41(2), 175–182. https://doi.org/10.3881/j.issn.1000-503X.10872
Additional referenced studies that reinforce the significance of this research could include:
1. Stewart, A. K., & Rajkumar, S. V. (2017). Multiple Myeloma: Defining the Role of New Therapies. Blood Journal, DOI: 10.1182/blood-2010-04-189977
2. Neri, P., Ren, L., Azab, A. K., Brentnall, M., Gratton, K., Klimowicz, A. C., et al. (2011). Integrative Profiling of Gene Expression and DNA Copy Number Identified RPS9 as a Potential Candidate Gene in Multiple Myeloma. Genes, Chromosomes and Cancer, DOI: 10.1002/gcc.20884
3. Teoh, P. J., & Chng, W. J. (2014). p53 Abnormalities and Potential Therapeutic Targeting in Multiple Myeloma. Journal of Hematology & Oncology, DOI: 10.1186/s13045-014-0094-z
4. Li, Z., & Xu, M. (2017). The Role of NF-κB in the Pathogenesis of Multiple Myeloma. Journal of Hematology & Oncology, DOI: 10.1186/s13045-017-0428-7
5. Hideshima, T., & Anderson, K. C. (2019). Molecular Mechanisms of Novel Therapeutic Approaches for Multiple Myeloma. Nature Reviews Cancer, DOI: 10.1038/nrc2684
Keywords
1. Multiple Myeloma Targeted Therapy
2. RPS9 Expression Multiple Myeloma
3. NF-kB Signaling Pathway Cancer
4. Myeloma Cell Apoptosis Proliferation
5. Ribosomal Proteins Oncology Research