High level of RNF187 contributes to the progression and drug resistance of osteosarcoma

Abstract

Objectives: Ring finger protein 187 (RNF187) was recently demonstrated to be up-regulation and function as a promoter in multiple cancers. However, the roles of RNF187 in osteosarcoma (OS) are unclear. Here, we tried to reveal the clinicopathological and biological roles of RNF187 in OS. Materials and Methods:We employed the quantitative real-time polymerase chain reaction (qRT-PCR) and immunohistochemistry (IHC) to determine the expression of RNF187 in OS tissues and cells. Migration and invasion capacities were analyzed by wound healing and transwell assays, and colony formation and CCK8 assays were performed to investigate proliferative ability. The functional effects of RNF187 on OS drugs resistance were further determined by CCK8 and western blot assays. Then, the relationship between RNF187 expression and clinical implications was analyzed by tissue microarrays (TMAs) including 51 OS cases. Moreover, the prognostic value was also determined by Kaplan-Meier analysis. Results: We reported that RNF187 mRNA was significantly increased in OS tissues compared to matched nontumorous tissues (3.83 ±0.79 vs. 1.70 ± 0.63), which was in line with the IHC assay in TMAs. By RNA interference and cDNA transfection, we showed high level of RNF187 increased the migration, invasion and proliferation of OS cells. Moreover, we demonstrated that elevated RNF187 expression induced OS cell drugs resistance, activated the ERK1/2 molecular and markedly enhanced the BCL-2 expression. Clinically, OS patients with high level of RNF187 was associated with Histologic differentiation (p=0.001), an advanced Enneking stage (p=0.001), response to chemotherapy (p=0.004), and metastasis (p= 0.001). Clinically, our data displayed that the RNF187 overexpression in OS samples associated with shorten overall survival (p=0.001) and high tumor recurrence (p=0.001) in postoperative OS patients. Conclusions:Our results indicate that Elevated RNF187 expression is a new adverse outcomes marker for OS patients and may be used as a new therapeutic target of OS.

MUC 15 Promotes Osteosarcoma Cell Proliferation, Migration and Invasion through Livin, MMP-2/MMP-9 and Wnt/β-Catenin Signal Pathway

“…International Publisher mechanisms through individual diagnosis, such as gene sequencing and chemotherapeutic drug screening. Great progress has been reported that chromosome abnormality, tumor suppressor gene abnormality, transcription factor, growth factor, WWOX and miRNAs play important roles in the occurrence and development of OS [8][9][10][11][12][13][14][15][16]. However, the above research is still in its infancy in use, and there is no sufficient evidence to show that patients' benefit from it.…”

Dysregulation of miR-144-5p/RNF187 axis contributes to the progression of colorectal cancer

“…The role of RNF187 in different tumours remains controversial. While RNF187 exhibits tumour-suppressive activities in oesophageal squamous cell carcinoma [ 22 ] and triple-negative breast cancer, [ 19 ] ectopic RNF187 expression predicts a poor outcome and contributes to tumour progression in lung cancer, [ 16 ] hepatocellular carcinoma, [ 17 ] osteosarcoma [ 26 ] and ovarian carcinoma. [ 27 ] This discrepancy may be due to the differential substrates targeted by RNF187 in different cell types.…”

“…RING finger protein 187 (RNF187), also known as RACO-1, belongs to the RING domain-containing protein family. It functions as an E3 ligase to modulate various cellular processes involved in malignant neoplasms including lung cancer, [ 16 ] hepatocellular carcinoma, [ 17 ] osteosarcoma [ 18 ] and breast cancer. [ 19 ] RNF187 forms a homodimer in nuclear specifically interacting with c-Jun, which is required for c-Jun/activator protein 1 (AP-1)-activated gene transcription.…”

Circular RNA hsa_circ_0000915 promotes propranolol resistance of hemangioma stem cells in infantile haemangiomas

“…RNF187, a E3 ubiquitin ligase to enable ubiquitin-protein transferase activity, has been widely reported to be an oncogene in multiple cancer types. For example, Chen et al demonstrated overexpression of RNF187 induced cell EMT and apoptosis resistance in NSCLC [ 49 ]; Shi et al revealed high level of RNF187 contributed to progression and drug resistance of osteosarcoma [ 50 ]; Liu et al identified an essential oncogenic role of RNF187 in metastasis of hepatocellular carcinoma [ 51 ]. All these previous literatures strongly implied Circ_0000915 may play a pivotal role in IHs, which has driven us to make a further study in this work.…”