Hypoxia-induced let-7f-5p/TARBP2 feedback loop regulates osteosarcoma cell proliferation and invasion by inhibiting the Wnt signaling pathway

Abstract

Osteosarcoma (OS) is the most common bone tumor in children and adolescents and is characterized by high metastatic and recurrence rates. In the past, it has been shown that microRNAs may play critical roles in hypoxia-related OS proliferation and invasion. However, the mechanisms by which OS cells acquire this malignant phenotype have remained largely unknown. In the present study, we report that let-7f-5p and TARBP2 were expressed in lower amounts in human OS cell lines when compared with the hFOB normal human osteoblastic cell line; however, both types of cells were repressed by hypoxia. let-7f-5p and TARBP2 significantly inhibited the proliferation and invasion of OS cells. Furthermore, TARBP2 as a downstream and functional target of let-7f-5p regulated the expression of let-7f-5p, and there was a regulatory feedback loop between let-7f-5p and TARBP2. This loop reduced the expression of let-7f-5p and TARBP2 in OS cells to a very low level, which was induced by hypoxia. Furthermore, the hypoxia-induced let-7f-5p/TARBP2 feedback loop contributed to activation of the Wnt signaling pathway. Taken together, our data clearly showed that the feedback loop between let-7f-5p and TARBP2 induced by the hypoxia-promoted OS cell malignant phenotype increased with activation of the Wnt signaling pathway.

Employing hypoxia characterization to predict tumour immune microenvironment, treatment sensitivity and prognosis in hepatocellular carcinoma

“…Hypoxia is an important factor to promote tumour cell proliferation and tumour progression. Meanwhile, hypoxia is related to maintaining the malignant phenotype of tumour [6] . Recently, the association between hypoxia and tumour microenvironment (TME) has received increasing attention.…”

Characterization of the microRNA Transcriptomes and Proteomics of Cochlea Tissue-derived Small Extracellular Vesicles From Different Age of Mice After Birth

“…3b, c). Of the increased miRNAs, miRLet-7f-5p [44], miRLet-7e-5p [45], miRLet-7c-5p [46], miR29a-3p [47], miR146b-5p [48], miRLet-7d-5p [49], miR338-3p [50], miR144-3p [51], miRLet-7j [52], miR449a-5p [53], miR30c-1-3p [54], miR147-3p [55], miR30c-2-3p [56], and miR1195 [57] have been attributed to a range of biological processes including cellular proliferation, cellular differentiation, and cellular signaling and communication. The miRNAs miR3074-1-3p, miR3095-3p, miR344b-3p, and miR3057-5p have no reported biological functions.…”

The Landscape of Regulatory Noncoding RNAs in Ewing’s Sarcoma

“…For example, the EWS protein is responsible for deregulating metaphase activity in mitosis via an up regulatory interaction with the Aurora-B kinase, which is a suspected oncogenic mechanism [100,101]. The tumor suppressor miRNA let-7f was found to target Aurora-B to reduce proliferation, invasion and migration but was only researched in OS [102]. Given that OS is related to ES, it seems plausible that let-7f may be downregulated in ES given a shared mechanism between the two; however, this link has not been reported in the current research.…”