CIP2A regulates proliferation and apoptosis of multiple myeloma cells

Abstract

Multiple myeloma (MM) is one of the most common causes of mortality from hematological malignancy in China. Recent studies have demonstrated that cancerous inhibitor of protein phosphatase 2A (CIP2A) may exhibit a role in promoting the growth of cancer; however, the function of CIP2A in MM remains unknown. In the present study, the expression and molecular mechanism underlying the effects of CIP2A in patients with MM and in MM cell lines were elucidated. Firstly, the expression of CIP2A was detected in patients with MM and in MM cell lines by reverse transcription‑quantitative polymerase chain reaction. Furthermore, silencing of CIP2A with short hairpin RNA was performed in MM cells, and the impact on the proliferation and apoptosis of RPMI‑8226 cells was analyzed (as endogenous CIP2A is highly expressed in RPMI‑8226 cell lines compared with other cells). CIP2A was significantly elevated in patients with MM and in MM cell lines, and silencing of CIP2A could inhibit the proliferation ability of RPMI‑8226 cells in vitro. In addition, CIP2A knockdown induced apoptosis and led to substantial reduction of c‑Myc protein levels in MM cell lines. This study suggested that CIP2A inhibition may provide a promising therapeutic strategy for patients with MM.

MicroRNA-383-5p acts as a prognostic marker and inhibitor of cell proliferation in lung adenocarcinoma by cancerous inhibitor of protein phosphatase 2A

“…CIP2A, also known as KIAA1524 and p90, is implicated as a human oncoprotein that promotes the stability of c-Myc protein and inhibits the degradation of c-Myc by inhibiting the protein phosphatase 2A-mediated dephosphorylation of Myc at Ser 62 ( 28 ). A number of studies have documented that CIP2A serves an important role in cell proliferation ( 29 ), transformation ( 30 ), drug resistance ( 31 ) and maintenance of a malignant cellular phenotype ( 32 ). Furthermore, CIP2A status was a significant prognostic factor for patients with non-small cell carcinoma, and CIP2A protein expression levels were revealed to be overexpressed in human lung cancer samples and associated with poor survival rates ( 33 ).…”

The role of CIP2A as a therapeutic target of rapamycin in radioresistant head and neck cancer with TP53 mutation

“…Accumulating evidence indicates that CIP2A overexpression is associated with poor survival in patients with solid tumors and may serve as a predictive factor of poor prognosis. 10,15,25 Preclinical in vitro and in vivo studies have shown that CIP2A may regulate the proliferation, senescence, and apoptosis of multiple cancer cells [26][27][28] and contribute to resistance to chemotherapy such as cisplatin or docetaxel in solid tumors. [29][30][31] Therefore, CIP2A inhibition may serve as a promising modality to overcome chemoresistance.…”

MicroRNA-518b functions as a tumor suppressor in glioblastoma by targeting PDGFRB

“…miR-518b has been deemed a tumor suppressor in carcinogenesis, as demonstrated by the observation that downregulation of miR-518b has frequently been detected in esophageal squamous cell carcinoma ( 17 ) and chondrosarcoma ( 18 ). In a recent study, a miRNA microarray demonstrated that miR-518b, which targets PDGFRB, is downregulated in microvascular proliferation, which may be the mechanism underlying the high expression of PDGFRB in GBM microvascular proliferation ( 19 ). The present study demonstrated that the expression of miR-518b was reduced in GBM tissues and cell lines.…”

“…PDGFRB, which is a cell-surface tyrosine kinase receptor, is an important target for anticancer therapeutics ( 19 , 21 ). It has been reported that PDGFRB is an angiogenic factor, which is implicated in numerous cellular processes, including angiogenesis, proliferation and migration ( 22 , 23 ).…”

“…Previous studies have suggested that PDGFRB may induce GBM tumorigenesis, and enhance tumor proliferation by modulating the expression of tumor suppressor miRNAs in U87 human GBM cells ( 21 , 24 ). Furthermore, the expression levels of PDGFRB are significantly increased in GBM microvascular proliferation than in GBM tumor cells indicating that PDGFRB serves a critical role in GBM microvascular proliferation ( 19 ). In the present study, dual-luciferase reporter assay and western blotting demonstrated that PDGFRB is a direct target of miR-518b, and PDGFRB is negatively regulated by miR-518b in GBM tissues.…”