A novel Twist1/hsa-miR138-5p/caspase-3 pathway regulates cell proliferation and apoptosis of human multiple myeloma.

Abstract	The nuclear transcription factor twist-related protein 1 (Twist1) is associated with tumor malignant transformation and metastasis in various types of carcinomas. We found that Twist1 was highly expressed in clinical multiple myeloma (MM) cells, and explored its roles in proliferation and apoptosis in human MM cell lines U266 and RPMI-8226. In these cells, Twist1 transcriptionally regulated the miRNA hsa-miR138-5p, which targeted caspase-3 to control apoptosis. Silencing of Twist1 significantly suppressed cell proliferation and increased apoptosis, which was reversed by overexpression of hsa-miR138-5p or simultaneous silencing of caspase-3. This reversion was further substantiated by attenuated apoptotic signaling, including downregulated expression of the cleaved forms of caspase-3 and peroxisome proliferator-activated receptor 1 (PPAR1). We demonstrate here for the first time that the novel Twist1/hsa-miR138-5p/caspase-3 pathway contributes significantly to the proliferation and survival of human MM cells. Our study provides new insight for novel MM treatments by developing Twist1-targeted therapeutics.
Authors	Wenjiao Qin, Qin Liu, Xiaoping Xu, Aiping Liu, Huating Zhang, Jingwen Gu, Tao Zhang
Journal	Annals of hematology (Ann Hematol) Vol. 100 Issue 7 Pg. 1815-1824 (Jul 2021) ISSN: 1432-0584 [Electronic] Germany
PMID	32388607 (Publication Type: Journal Article)
Chemical References	MIRN138 microRNA, human MicroRNAs Nuclear Proteins TWIST1 protein, human Twist-Related Protein 1 CASP3 protein, human Caspase 3
Topics	Aged Aged, 80 and over Apoptosis (genetics) Caspase 3 (genetics, physiology) Cell Line, Tumor Cell Movement (genetics) Cell Proliferation (genetics) Female Gene Expression Regulation, Neoplastic HEK293 Cells Humans Male MicroRNAs (genetics, physiology) Middle Aged Multiple Myeloma (genetics, pathology) Nuclear Proteins (genetics, physiology) Signal Transduction (genetics) Twist-Related Protein 1 (genetics, physiology)

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