2. Academic Validation
  3. The impact of STAiR18 on multiple myeloma survival rates

The impact of STAiR18 on multiple myeloma survival rates

  • J Transl Med. 2025 Nov 7;23(1):1243. doi: 10.1186/s12967-025-07210-x.
Yingmiao Wu # 1 2,  Haolin Wang # 1 2,  Ji Luo 1 2,  Jiaoya Lin 3 4,  Yajie Wu 1 2,  Shuai Zheng 1 2,  Yifei Gao 1 2,  Jiao Chen 5,  Feifei Che 5,  Jianyou Shi 6,  Ling Zhong 7
Affiliations

Affiliations

  • 1 Genetic Diseases Key Laboratory of Sichuan Province, Department of Medical Genetics, Department of Laboratory Medicine, Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China.
  • 2 School of Medicine, University of Electronic Science and Technology of China, Chengdu, Sichuan, China.
  • 3 Department of Clinical Laboratory Diagnosis, The Affiliated Hospital, Southwest Medical University, Luzhou, Sichuan, China.
  • 4 Department of Blood Transfusion, Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital, Chengdu, Sichuan, China.
  • 5 Department of Hematology, Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, Sichuan, China.
  • 6 Department of Pharmacy, Personalized Drug Therapy Key Laboratory of Sichuan Province, Sichuan Academy of Medical Sciences & Sichuan Provincial, People's Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, Sichuan, China. [email protected].
  • 7 Genetic Diseases Key Laboratory of Sichuan Province, Department of Medical Genetics, Department of Laboratory Medicine, Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China. [email protected].
  • # Contributed equally.
PMID: 41204251 DOI: 10.1186/s12967-025-07210-x
Abstract

Background: A subset of multiple myeloma (MM) patients exhibited worse survival and higher tumor burden. STAiR18 has been found to be highly expressed in MM cell lines. However, the precise mechanisms underlying the upstream and downstream regulation of STAiR18 have remained unclear.

Methods: The expression of STAiR18 and miR-451a in MM patients and cell lines was detected using quantitative Reverse Transcriptase PCR (qRT-PCR). ChIP-qPCR was performed to assess the enrichment of pSTAT3 at the STAiR18 promoter. The subcellular localization of STAiR18 was determined by FISH. The binding relationship between STAiR18 and miR-451a was predicted through bioinformatics analyses and validated using RNA pull down and dual-luciferase reporter assays. Cell proliferation was evaluated with CCK-8 assay, Edu assay, and flow cytometry. The expression levels of key proteins in the IL-6R/STAT3/JAK2 pathway, along with Cyclin D1 and apoptosis-related markers, were analyzed by Western blot. Cell cycle distribution and Apoptosis rate were quantified by flow cytometry. The role of STAiR18 was also investigated in vivo using a xenograft tumor model, which was established by tail vein injection of MM cell lines into NOG mice.

Results: In MM patients, STAiR18 expression was notably upregulated in myeloma cells from bone marrow, and positively correlated with clinical stage and worse outcome. Knockdown (KD) and overexpression (OE) of STAT3 affected the expression level of STAiR18, and pSTAT3 was significantly enriched in STAiR18's promoter. Knockdown of STAiR18 reduced the proliferation of MM cells in vitro and suppressed tumor growth in vivo. STAiR18 was predicted and confirmed to primarily localize in the cytoplasm. STAiR18 KD resulted in upregulation of miR-451a levels. The binding between STAiR18 and miR-451a (silencing IL-6R) was predicted and validated. Through KD and rescue experiments, we demonstrated that STAiR18 sponged miR-451a, and promoted myeloma cell proliferation via IL-6R/STAT3/JAK2 pathway.

Conclusions: The study revealed that STAiR18 competed with endogenous miR-451a, and formed a novel positive-feedback loop of IL-6R/STAT3/JAK2 to promote proliferation of MM. These findings suggest that STAiR18 represents a promising novel therapeutic strategy for MM treatment.

Keywords

IL-6R/STAT3/JAK2 pathway; Multiple myeloma (MM); Proliferation; STAiR18; miR-451a.

Figures
Products
Inhibitors & Agonists