SIRT2-KLF4 Interactions are Critical for Myeloma Survival and Migration

Abstract

Objective. To investigate the roles and possible mechanisms of SIRT2 and KLF4 in the development and progression of myeloma. Methods. Rt-PCR was used to detect SIRT2 in myeloma samples from patients and myeloma cells, the expression level of KLF4 in myeloma cells, and the effect of downregulation of SIRT2 expression on KLF4 expression level. MTT assay and wound-healing assay were used to observe the proliferation and migration of U266cells transient transfected with Sirt2 inhibitors. Results. SIRT2 is highly expressed in myeloma, but KLF4 was down. Downregulation of SIRT2 expression stimulated the expression level of KLF4. Reduced SIRT2 activity results in the release of KLF4 expression, which inhibits the proliferation and migration of myeloma cells. Conclusion. SIRT2-KLF4 combination plays an important role in the occurrence and development of myeloma.

The Role of Sirtuin 2 in Chemotherapeutic Resistance

“…es KLF4 expression and inhibits myeloma cell proliferation and migration. [5] In another multiple myeloma study, SIRT2 knockdown inactivated RAS/ERK signaling and cell proliferation. [10] Aldo-keto reductase family 1 member C1 (AKR1C1) is one of the promoting factors in malignancy.…”

“…[3] SIRT2 is a NAD-dependent deacetylase that is involved in various cellular processes including cell proliferation, cell death, cell migration and microtubule dynamics. [4,5] The physiological roles of SIRT2 differ according to cell types. SIRT2 has been reported to be both oncogenic and tumor suppressive.…”

Ginsenoside Rh4 inhibits the malignant progression of multiple myeloma and induces ferroptosis by regulating SIRT2

“…It was reported that the knockdown of SIRT2 could inhibit cell proliferation and RAS/extracellular‐signal‐regulated kinase (ERK) signalling, but promote cell apoptosis and cell cycle arrest in MM 10 . The reduced SIRT2 activity could stimulate Krüppel‐like factor 4 (KLF4) expression and inhibit the proliferation and migration of myeloma cells 11 . However, whether ginsenoside Rh4 can regulate the malignant progression of MM and cell ferroptosis by targeting SIRT2 still needs to be confirmed.…”

“…10 The reduced SIRT2 activity could stimulate Krüppel-like factor 4 (KLF4) expression and inhibit the proliferation and migration of myeloma cells. 11 However, whether ginsenoside Rh4 can regulate the malignant progression of MM and cell ferroptosis by targeting SIRT2 still needs to be confirmed.…”