Researchers from the School of Biological Sciences (SBS) have made a breakthrough in understanding why some multiple myeloma patients stop responding to treatment. Their study, published in Nature Communications (1 September 2025), identifies a novel long non-coding RNA that helps cancer cells survive chemotherapy, opening new avenues for potential therapies.
The research was led by Nanyang Assistant Professor Li Yinghui, with Dr. Kamalakshi Deka, Research Fellow in Li’s lab, as the lead author. The team’s achievement highlights the impact of their work in RNA biology, structural prediction, and epigenetics applied to cancer research.
Why Drug Resistance in Multiple Myeloma is a Major Challenge
Multiple myeloma is a cancer of plasma cells that often responds to standard treatments such as bortezomib, lenalidomide, and dexamethasone (VRd). Over time, however, many patients develop resistance to these drugs, leaving limited treatment options and making the disease harder to manage. Understanding the molecular mechanisms behind this resistance is crucial for developing more effective treatments for relapsed and refractory multiple myeloma.
PLUM: A Novel RNA Driving Chemoresistance
The team discovered a previously uncharacterised long non-coding RNA (lncRNA) named PLUM, which is upregulated in high-risk and treatment-refractory multiple myeloma patients. In this study, lead author Dr Kamalakshi Deka and colleagues reported a new function for PLUM in promoting chemoresistance through its interaction with EZH2, a protein subunit of the Polycomb Repressor Complex 2 (PRC2), an epigenetic regulator that can modulate gene expression in multiple myeloma cells.
[Image from Nature Communications, Fig. 7n] Graphical representation of the working model: PLUM-EZH2 interaction drives formation of PRC2 complex altering stability and activity of EZH2 to mediate repression of tumour suppressor genes (FOXO3 and ZFP36), in turn inducing UPR pathway and confers chemoresistance in MM. Created in BioRender. Deka, K. (2025) https://BioRender.com/x1ek3vo.
This multidisciplinary project utilised a variety of cutting-edge, innovative tools in RNA biology, structural prediction, and epigenetics to characterise a critical function of a long non-coding RNA in cancer and explored the use of nucleic acid therapeutics as a promising strategy for future cancer treatments.
Opening New Avenues for Future Cancer Therapies
This study highlights the importance of understanding RNA-mediated mechanisms in cancer and provides a promising strategy for developing nucleic acid–based therapies for drug-resistant multiple myeloma. By combining RNA biology, epigenetic insights, and structural prediction, the team has opened new avenues for targeted, innovative cancer therapies.
Congratulations to Asst. Prof. Li Yinghui, Dr. Kamalakshi Deka, and the SBS team – Jean-Michel Carter, Akash Bahai, Daniel Aron Ang, Nicholas Sim, Guan Hwee Bernard Lee, and Assoc. Prof. Tan Suet Mien for this impactful achievement, together with their collaborators.
Read the full paper here.