Silencing of Y-box binding protein-1 by RNA interference inhibits proliferation, invasion, and metastasis, and enhances sensitivity to cisplatin through NF-κB signaling pathway in human neuroblastoma SH-SY5Y cells

Abstract

Y-box binding protein-1 (YB-1), a member of Y-box protein family binding DNA and RNA, has been proposed as a novel marker in multiple malignant tumors and found to be associated with tumor malignancy. Neuroblastoma is an embryonal tumor arising from neuroblast cells of the autonomic nervous system, which is the most common cancer diagnosed in infants. It has been reported that YB-1 is highly expressing in various human tumors including nasopharynx, thyroid, lung, breast, colon, ovary, and prostate cancers. This study aimed to investigate the functional role of YB-1 in neuroblastoma by silencing YB-1 using RNA interference (shRNA) in neuroblastoma SH-SY5Y cells. We found that silencing of YB-1 decreased the proliferation, migration, and invasion of SH-SY5Y cells. At molecular level, inhibition of YB-1 decreased the expression level of PCNA as well as MMP-2 in neuroblastoma SH-SY5Y cells. Also, we discovered that YB-1 silencing sensitized SH-SY5Y cells to cisplatin and promoted the apoptosis induced by cisplatin due to down-regulation of multidrug resistance (MDR) 1 protein via NF-κB signaling pathway. Therefore, we consider that targeting YB-1 is promising for neuroblastoma treatment and for overcoming its cisplatin resistance in the development of new neuroblastoma therapeutic strategies.

Proteomic Signature of Neuroblastoma Cells UKF-NB-4 Reveals Key Role of Lysosomal Sequestration and the Proteasome Complex in Acquiring Chemoresistance to Cisplatin

“…Nbl accounts for 7% of malignancies from birth to 14-y of age 4 and 12% of cancer deaths in children. Biology of Nbl is heterogeneous, only a minimal number of Nbl regress spontaneously, while in the majority of the cases, the development of a malignant phenotype characterized by aggressive behaviour with metastasis results in mortality of more than 50% of the chemoradiotherapy-treated patients [5][6][7][8] .…”

Critical Role for Cold Shock Protein YB-1 in Cytokinesis

“…In addition, reducing YB-1 levels in tumour xenograft models of breast, brain, lung and pharyngeal cancers inhibited cell proliferation [ 4 , 8 , 9 ]. Furthermore, YB-1 has also been implicated in regulating the proliferation of breast cancer, large B-cell lymphoma, lung adenocarcinoma, neuroblastoma, hepatocellular carcinoma, glioma, renal cell carcinoma and melanoma in vitro [ 4 , 10 , 11 , 12 , 13 , 14 , 15 , 16 ]. YB-1 has been implicated in regulating many genes involved in proliferation [ 10 , 11 , 12 , 13 , 14 , 15 ] and survival, reviewed in [ 1 , 17 ], including the 70-gene breast cancer “signature” [ 18 ] and the E2F family gene cluster [ 4 ].…”

Mechanisms of tRNA-derived fragments and tRNA halves in cancer treatment resistance

“…YBX1 is overexpressed in multiple cancers [53] and enhances chemoresistance in melanoma [92], embryonal rhabdomyosarcoma [93], NSCLC [94], prostate cancer [95], gastric cancer [96], breast cancer [97], neuroblastoma [53], hepatocellular carcinoma [98], ovarian carcinoma [99], bladder cancer [100], diffuse large B-cell lymphoma [101], prostate cancer [102], chordomas [103], and esophageal squamous cell carcinoma (ESCC) [104]. YBX1 promotes cancer chemoresistance by upregulating ABC transporters related to multidrug resistance [53,94,97,104,105]. Overexpression of YBX1 confers resistance to mitoxantrone by cell adhesion mechanisms in diffuse large B-cell lymphoma [101].…”

“… [ 18 ] tRF-2 derived from tRNA Glu , tRNA Asp , tRNA Gly and tRNA Tyr tRFs increase chemosensitivity of various tumors by replacing 3′-UTR from YBX1. [ 23 , 53 ] ts-46, ts-47 ts-46 and ts-47 are upregulated by PIK3CA and KRAS mutations, respectively. These two mutations are involved in the resistance of breast cancer cells to lapatinib.…”