microRNA‐196a‐5p inhibits testicular germ cell tumor progression via NR6A1/E‐cadherin axis

Abstract

Testicular germ cell tumors (TGCTs) are a diverse group of neoplasms that are derived from dysfunctional fetal germ cells and can also present in extragonadal sites. The genetic drivers underlying malignant transformation of TGCTs have not been fully elucidated so far. The aim of the present study is to clarify the functional role and regulatory mechanism of miR‐196a‐5p in TGCTs. We demonstrated that miR‐196a‐5p was downregulated in TGCTs. It can inhibit the proliferation, migration, and invasion of testicular tumor cell lines including NT‐2 and NCCIT through targeting the NR6A1 gene, which we proved its role in promotion of cell proliferation and repression of cellular junction and aggregation. Mechanistically, NR6A1 inhibited E‐cadherin through binding with DR0 sites in the CDH1 gene promoter and recruiting methyltransferases Dnmt1. Further, NR6A1 promoted neuronal marker protein MAP2 expression in RA‐induced neurodifferentiation of NT‐2 cells and testicular tumor xenografts. Clinical histopathologically, NR6A1 was positively correlated with MAP2, and negatively correlated with E‐cadherin in TGCTs. These findings revealed that the miR‐196a‐5p represses cell proliferation, migration, invasion, and tumor neurogenesis by inhibition of NR6A1/E‐cadherin signaling axis, which may be a potential target for diagnosis and therapy of TGCTs.

The diagnostic and prognostic values of microRNA-196a in cancer

“…Previous studies have shown that miR-196a, acts as an oncogene, exert multiple functions in carcinogenesis and cancer progression, such as down-regulation of miR-196a inhibited proliferation and invasion of hepatocellular carcinoma (HCC) cells by targeting FOXO1 [ 4 ]; in breast cancer, overexpression of miR-196a promotes tumor growth and metastasis by targeting SPRED1 [ 5 ]; in osteosarcoma, it could promote cell migration, invasion and the epithelial–mesenchymal transition by targeting HOXA5 [ 6 ]. Whereas, in testicular germ cell tumor, it was also reported to repress cell proliferation, migration, invasion and tumor neurogenesis by inhibition of NR6A1/E-cadherin signaling axis [ 7 ]. Moreover, in head and neck cancer, cancer-associated fibroblasts derived exosomal miR-196a was responsible for cisplatin resistance by targeting CDKN1B and ING5 [ 8 ].…”

Chromodomain helicase DNA-binding domain 2 maintains spermatogonial self-renewal by promoting chromatin accessibility and mRNA stability

“…The ChIP experiments were performed according to the literature. 65 After transfection with siNC or siCHD2 for 48 h, C18-4 cells were cross-linked with 1% formaldehyde for 10 min at 37°C, terminated by 0.125 mol/L glycine at room temperature and then lysed by SDS lysis. Samples were sonicated at 30% power with a 5 s pulse and 5 s intervals at 4°C for 8 min using a Bioruptor Pico (Diagenode s.a., Seraing, Belgium) to obtain 200∼1000 bp fragments.…”

Inorganic biomaterials‐based bioinks for three‐dimensional bioprinting of regenerative scaffolds

“…[ 35 ] By adding an appropriate amount of inorganic biomaterials, the ions can be released from the bioinks in a controlled manner. [ 36 ] Therefore, the ions released by inorganic biomaterials contribute to the gelation of the hydrogels and adjust the cross‐linking process, thereby improving the printing fidelity. Accordingly, kinds of inorganic biomaterials were added into the bioinks to modify the hydrogel for improving the printing fidelity.…”