HIF-1α suppresses myeloma progression by targeting Mcl-1

Area of Science:

• Oncology
• Molecular Biology
• Cancer Research

Background:

• The role of Hypoxia-inducible factor 1-alpha (HIF-1α) in cancer progression is established, but its specific function in multiple myeloma (MM) remains unclear.
• Mcl-1 is implicated in cancer cell survival and drug resistance.

Purpose of the Study:

• To elucidate the role of HIF-1α in multiple myeloma (MM) pathogenesis.
• To investigate the relationship between HIF-1α and Mcl-1 in MM cells.

Main Methods:

• Quantitative reverse transcription polymerase chain reaction (qRT-PCR) and cell counting kit-8 (CCK-8) assays were used to assess gene expression and cell proliferation.
• The Gene Expression Omnibus (GEO) database was utilized to analyze Mcl-1 expression in MM patient samples.
• Experiments involved silencing HIF-1α and Mcl-1 expression, as well as Mcl-1 overexpression.

Main Results:

• Silencing HIF-1α and Mcl-1 decreased MM proliferation and induced apoptosis.
• Mcl-1 expression was found to be elevated in MM samples.
• Overexpression of Mcl-1 counteracted the anti-proliferative and pro-apoptotic effects of HIF-1α silencing.
• HIF-1α was identified as a direct transcription factor targeting the Mcl-1 promoter, thereby upregulating its expression.

Conclusions:

• HIF-1α plays a crucial role in the progression of multiple myeloma.
• HIF-1α directly regulates Mcl-1 expression, contributing to MM cell survival and proliferation.
• Targeting the HIF-1α/Mcl-1 axis presents a potential therapeutic strategy for multiple myeloma.