MicroRNA-643 regulates the expression of ZEB1 and inhibits tumorigenesis in osteosarcoma

Abstract

Osteosarcoma is among the most malignant types of tumor worldwide and has become a leading contributor to tumor incidence, particularly in adolescents. Resistance to conventional treatment and the complexity of osteosarcoma tumorigenesis has resulted in high mortality rates. MicroRNAs are a class of noncoding RNAs, which regulate numerous biological processes. However, the involvement of miR-643 in osteosarcoma remains to be elucidated. In the present study, reverse transcription-quantitative polymerase chain reaction, luciferase reporter assay, invasion assay, viability assay, western blot analysis and in vivo implantation were performed to analyze the action of miR-643 in osteosarcoma. The results demonstrated that miR-643 inhibited the progression of osteosarcoma and acted as a potential tumor suppressor. The expression of miR-643 was downregulated in osteosarcoma tissues and cell lines. In addition, miR-643 transfection significantly impaired the proliferation and invasion of osteosarcoma cells. The present study also identified Zinc finger E-box-binding homeobox 1 (ZEB1) as a direct target of miR-643, and the ectopic expression of ZEB1 counteracted the effect of miR-643 transfection. A significant inverse correlation was also found between the expression of miR-643 and ZEB1. A low expression of miR-643 or a high expression of ZEB1 was associated with poor patient survival rates. The results of the present study suggested that the decreased expression of miR-643 may be involved in the mechanism underlying the development of osteosarcoma. The intricate interactions between miR-643 and ZEB1 may serve as a potential therapeutic target in osteosarcoma oncogenesis.

Naringin targets Zeb1 to suppress osteosarcoma cell proliferation and metastasis

“…Zeb1 was shown to promote the progression of lung cancer by increasing the expression of MMP2, a member of the matrix metalloproteinases family that play an important role in cell migration and facilitate invasion and metastasis of tumor cells [18,19]. Zeb1 has also been shown to be upregulated in osteosarcoma, and to contribute to its development [20,21].…”

MiR‐643 inhibits lipopolysaccharide‐induced endometritis progression by targeting TRAF6

“…As we know, the function of miRNA is realized by regulating target expression in cancers and diseases. Previous studies have indicated many targets of miR‐643, including X‐linked inhibitor of apoptosis protein and zinc finger E‐box binding homeobox transcription factor 1 (Wang et al, 2017; Lopez‐Rosas et al, 2018). In this study, we first demonstrated TRAF6 as a target of miR‐643, which was confirmed by luciferase reporter assay and RIP.…”

“…Besides, miR‐27a‐3p and miR‐124‐3p are also involved in endometritis development (Di Pietro et al, 2018). The increasing evidence disclose that miR‐643 is expressed and associated with the progression of multiple cancers or diseases, such as non‐small‐cell lung carcinoma, pancreatic cancer, osteosarcoma, and colon parasites infection (Sun et al, 2013; Shen et al, 2015; Wang et al, 2017; Lopez‐Rosas et al, 2018). More importantly, a previous study shows that 23 miRNAs were abnormally expressed in endometritis, in which miR‐643 expression is decreased the most but miR‐215 (Hailemariam et al, 2014).…”

Entamoeba histolytica Up-Regulates MicroRNA-643 to Promote Apoptosis by Targeting XIAP in Human Epithelial Colon Cells

“…Previously, it was reported that miR-643 functions as a tumor suppressor gene in osteosarcoma cells. It was showed that miR-643 suppressed the cancer hallmarks and as a bona fide tumor suppressor it may also activates apoptosis (Wang et al, 2017). XIAP has a central regulatory role in programmed cell death by inhibiting the caspases cascade (Deveraux and Reed, 1999).…”