Long non-coding RNAs and therapeutic resistance in multiple myeloma - from molecular insights to clinical applications

Sep 22, 2026

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Multiple myeloma (MM) is a complex hematologic malignancy driven by abnormal plasma cell proliferation in the bone marrow. Despite therapeutic advances, drug resistance continues to block durable cures. This review summarizes how long non-coding RNAs (lncRNAs) regulate MM biology and shape treatment response, covering miRNA sponging, epigenetic modulation, apoptosis, and signaling crosstalk including PI3K/Akt and STAT3. It also assesses lncRNA-targeting strategies such as RNA therapeutics, CRISPR/Cas9, and exosome-mediated delivery, highlighting their potential to overcome resistance and support clinical translation. By linking molecular findings to clinical relevance, it proposes lncRNAs as biomarkers and therapeutic targets and outlines directions for future research and development.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages23

Reading Time58 min

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Clinical and Experimental Medicine (2026) 26:114 [https://doi.org/10.1007/s10238-025-02015-0](https://doi.org/10.1007/s10238-025-02015-0) REVIEW Long non-coding RNAs and therapeutic resistance in multiple myeloma: from molecular insights to clinical applications Mohamad Hosein Safari1 · Najma Farahani2 · Amirhossein Faghih Ojaroodi3 · Amirali Ebrahimpour4 · William C. Cho5 · Fateme Zare Khormizi6 · Alireza Mafi7 · Rasoul Raesi8,9 · Maryam Mohammad-Sadeghipour10 · Mina Alimohammadi11 · Kiavash Hushmandi12 · Mehrdad Hashemi2,13 · Afshin Taheriazam2,14 Received: 4 October 2025 / Accepted: 16 December 2025 © The Author(s) 2026 Abstract Multiple myeloma (MM) is a complex hematologic malignancy characterized by the abnormal proliferation of plasma cells in the bone marrow. Despite advances in therapy, resistance remains a significant obstacle to curing the disease. Long non-coding RNAs (lncRNAs), a broad family of regulatory RNA molecules, have recently been recognized as important players in MM biology, influencing disease progression and treatment response. This review explores current insights into the diverse roles of lncRNAs in MM, focusing on their involvement in key molecular processes, including miRNA sponging, epigenetic regulation, apoptosis, and interactions with signaling pathways such as PI3K/Akt and STAT3. Additionally, the review evaluates emerging treatment strategies targeting lncRNAs, including RNA-based therapeutics, CRISPR/Cas9 technology, and exosome-mediated delivery systems, assessing their potential to overcome drug resistance and improve clinical outcomes. By integrating molecular research with clinical implications, this review emphasizes the promise of lncRNAs as biomarkers and therapeutic targets in MM and offers a framework for future research and development. Keywords Long non-coding RNA · Multiple myeloma · Drug resistance · Signaling pathways · CRISPR/Cas9 · LncRNA-targeted therapy 􀀍 Maryam Mohammad-Sadeghipour [Maryam.ms160@gmail.com](Maryam.ms160@gmail.com) 􀀍 Mina Alimohammadi[mina.alimohammadi11@gmail.com](mina.alimohammadi11@gmail.com) 􀀍 Kiavash Hushmandi [houshmandi.kia7@ut.ac.ir](houshmandi.kia7@ut.ac.ir) 􀀍 Mehrdad Hashemi [mhashemi@iautmu.ac.ir](mhashemi@iautmu.ac.ir) 􀀍 Afshin Taheriazam[a.taheriazam@iautmu.ac.ir](a.taheriazam@iautmu.ac.ir) 1 Department of Internal Medicine, Faculty of Veterinary Medicine, University of Tehran, Tehran, Iran 2 Farhikhtegan Medical Convergence Sciences Research Center, Farhikhtegan Hospital, Faculty of Medicine, TeMs.C., Islamic Azad University, Tehran, Iran 3 Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran 4 Student Research Committee, Varastegan Institute for Medical Sciences, Mashhad, Iran 5 Department of Clinical Oncology, Queen Elizabeth Hospital, Kowloon, Hong Kong, China 6 Department of Biology, Yazd University, Yazd, Iran 7 Department of Genetics and Biochemistry, School of Medicine, Arak University of Medical Sciences, Arak, Iran 8 Department of Public Health, School of Health, Torbat Jam Faculty of Medical Sciences, Torbat Jam, Iran 9 Department of Public Health, School of Health, Mashhad University of Medical Sciences, Mashhad, Iran 10 Occupational Safety and Health Research Center, NICICO, World Safety Organization, Rafsanjan University of Medical Sciences, Rafsanjan, Iran 11 Department of Immunology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran 12 Nephrology and Urology Research Center, Clinical Sciences Institute, Baqiyatallah University of Medical Sciences, Tehran, Iran 13 Department of Genetics, Faculty of Advanced Science and Technology, TeMs.C., Islamic Azad University, Tehran, Iran 14 Department of Orthopedics, Faculty of Medicine, TeMs.C., Islamic Azad University, Tehran, Iran 1 3 Abbreviations ABC ABCG2 AKT ALL AML ANRIL ASO Bax Bcl-2 Cas9 CASC15 CCAT1 CDK ceRNACLLCML CRISPR ECC EMT

FAQs

What role do long non-coding RNAs (lncRNAs) play in multiple myeloma?

lncRNAs are described as regulatory RNA molecules that influence multiple myeloma progression and treatment response through mechanisms such as miRNA sponging, epigenetic regulation, apoptosis, and signaling interactions.

Which signaling pathways are highlighted as being influenced in multiple myeloma by lncRNAs?

The review specifically mentions interactions with pathways such as PI3K/Akt and STAT3 as part of how lncRNAs affect disease biology.

What therapeutic strategies targeting lncRNAs are evaluated to address drug resistance?

The review evaluates RNA-based therapeutics, CRISPR/Cas9 approaches, and exosome-mediated delivery systems, focusing on their potential to overcome drug resistance and improve clinical outcomes.

Sep 22, 2026

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