High expression of HOXC6 predicts a poor prognosis and induces proliferation and inflammation in multiple myeloma cells

• Published in: Genes & genomics Vol. 45; no. 7; pp. 945 - 955
• Main Authors: Li, Zhihua, Wang, Yaru, Hou, Xiaoxu, Guo, Luyao, Li, Yanling, Ma, Yanping
• Format: Journal Article
• Language: English
• Published: Singapore Springer Nature Singapore 01-07-2023; Springer; Springer Nature B.V; 한국유전학회
• Subjects: Adult; Analysis; Animal Genetics and Genomics; Apoptosis; Biomedical and Life Sciences; Cancer; Cell proliferation; Cell Proliferation - genetics; Cell viability; Cholecystokinin; Flow cytometry; Genetic aspects; Hemoglobin; Homeobox; Homeodomain Proteins - genetics; Homeodomain Proteins - metabolism; Human Genetics; Humans; Hyperplasia; Immunohistochemistry; Inflammation; Interleukin 6; Interleukin 8; Life Sciences; Medical prognosis; Microbial Genetics and Genomics; Multiple myeloma; Multiple Myeloma - genetics; Multiple Myeloma - metabolism; NF-kappa B - genetics; NF-kappa B - metabolism; NF-κB protein; Peripheral blood; Plant Genetics and Genomics; Prognosis; Reseach Article; Tumor necrosis factor-α; Tumorigenicity; Tumors; 생물학; TNF-α; IL-8; IL-6; Multiple myeloma; NF-κB pathway; HOXC6
• ISSN: 1976-9571; 2092-9293; 2092-9293
• DOI: 10.1007/s13258-023-01397-3

Background
Multiple myeloma (MM) is a common blood system malignance accompanied by monoclonal plasma cell hyperplasia. Homeobox C6 (HOXC6) acts as an oncogene in various cancers, but its function on MM is elusive.
Objective
The role of HOXC6 on MM development was clarified in this study.
Methods
HOXC6 expression and its clinical significance were determined in the peripheral blood samples collected from forty MM patients and thirty healthy adult volunteers. The overall survival was evaluated by Kaplan-Meier analysis with the log-rank test. Cell viability, proliferation and apoptosis were measured by CCK-8, EdU assay and Flow cytometry in U266 and MM.1R cells. Tumor growth was estimated by a xenograft assay. The apoptosis of tumor tissues was evaluated using TUNEL staining. The protein level in tissues was tested by immunohistochemistry.
Results
The HOXC6 expression was elevated in MM and high HOXC6 level was associated with the poor overall survival of MM. Besides, the HOXC6 expression was associated with hemoglobin level and ISS stage. Furthermore, silencing HOXC6 suppressed cell proliferation, induced cell apoptosis, and restrained the secretion of inflammatory factors (TNF-α, IL-6, and IL-8) in MM cells through inactivating the NF-κB pathway. Moreover, silencing HOXC6 suppressed the tumor growth of MM, the inflammatory factors levels, and the activation of NF-κB pathway but enhanced apoptosis in vivo.
Conclusion
HOXC6 was elevated in MM and associated with poor survival. Knockdown of HOXC6 suppressed proliferation, inflammation and tumorigenicity of MM cells via inactivating the NF-κB pathway. HOXC6 may be a meaningful target for MM therapy.