MiR-890 inhibits proliferation and invasion and induces apoptosis in triple-negative breast cancer cells by targeting CD147

Abstract

Background Triple-negative breast cancer (TNBC) is a type of breast cancer with a high degree of malignancy. Because of the remarkable biological characteristics of high invasion, metastasis and recurrence, TNBC is often accompanied by a poor prognosis. As a molecular characteristic of TNBC, high expression of CD147 has been confirmed by a large number of studies. However, the mechanism of CD147 expression regulation in TNBC remains elusive. In this study, we investigated the roles of miR-890 in inhibiting CD147. Methods Quantitative Reverse Transcription-Polymerase Chain Reaction (qRT-PCR) was used to detect CD147 mRNA and miR-890 level, and western blotting was used to detect CD147 protein. Bioinformatics screening and 3′-Untranslated Region (3′-UTR) luciferase assays were used to analyze the microRNAs (miRNA) binding site. Cell proliferation, apoptosis and invasion were assessed by using CCK-8, flow cytometry and transwell assays. Results The upregulation of miR-890 inhibited cell proliferation and invasion, induced apoptosis in MDA-MB-231 and HCC-70 TNBC cells by negatively regulating its target gene, CD147, and the upregulation of CD147 rescued the inhibitory effects of miR-890. miR-890 targeted CD147 by binding to its 3′-UTR. Further results showed that the upregulation of miR-890 also inhibited the expression of MMPs, the downstream genes of CD147, and promoted the cleavage of Caspase-3. The CD147 recovery experiment was further confirmed by the activity changes in the downstream MMPs of CD147. In addition, it was confirmed that the effect of CD147 in promoting TNBC cell proliferation and invasion, inhibiting apoptosis was related to the change in caspase-3 activity. Conclusion The downregulation of miR-890 is the potential cause of high CD147 expression in TNBC, which can promote the malignant transformation of TNBC.

Ribosomal protein S3 regulates XIAP expression independently of the NF-κB pathway in breast cancer cells

“…The expression of XIAP is known to be regulated at the protein level in various manners. For example, many microRNAs suppress the translation of XIAP (32)(33)(34)(35)(36) and the E3 ligase TRIM32 degrades the XIAP protein (37). In addition, the TRIP-Br1 and TRIP-Br3 proteins inhibit the degradation of XIAP (38) and a novel mechanism for XIAP degradation through an autophagy pathway has been identified (39).…”

Identification of Acute Myeloid Leukemia Bone Marrow Circulating MicroRNAs

“…Among the miRNAs that were expressed in HD but undetectable in patients, we found miR-448, miR-890 and miR-504. These miRNAs have been shown to be downregulated and function as tumor suppressors in several types of cancer [ 24 , 25 ]. Recently, miR-504 was shown to be significantly downregulated in the serum of AML patients and cell lines, and its overexpression inhibits cell growth and induces apoptosis in leukemic cells [ 26 ].…”

MicroRNAs Involved in Carcinogenesis, Prognosis, Therapeutic Resistance, and Applications in Human Triple-Negative Breast Cancer

“…Oncogenic miRNAs miR-21 PTEN Promotes the tumor proliferation and inhibits cell apoptosis [90] miR-182 PFN1, RIP1 Promote the tumor proliferation, inhibit cell apoptosis and migration [115,168] miR-301b CYLD Inhibits cell apoptosis induced by 5-FU [169] miR-155-5p FOXO3A Promotes proliferation and reduces bufalin-induced apoptosis [170] miR-17-5p/20a DR4/DR5 Inhibit apoptosis [171] miR-429 XIAP Regulates apoptosis [172] Oncosuppressor miRNAs miR-200c XIAP Induces apoptosis [126] miR-31 Bcl-2, PKCε Induce apoptosis, increase sensitivity of chemo-and radiosensitivity [173] miR-4458 SOCS1 Inhibits proliferation and promotes apoptosis [174] miR-890 CD147 Inhibits the cell proliferation and invasion, induces apoptosis [175] miR-509 TNF-α Increases apoptosis and inhibits invasion [176] miR-145 cIAP1 Promotes TNF-α-induced apoptosis [177] miR-199a-5p TGF-β2, PIK3CD Proliferate inhibition, cell cycle arrest, and increase apoptosis [83] miR-1296 CCND1 Suppresses proliferation, cell cycle arrest accompanied by induction of apoptosis [178] miR-10a PIK3CA Inhibits the proliferation and migration, promotes apoptosis [179] Oncosuppressive miRNAs are downregulated in TNBC to promote apoptosis through various signaling pathways, as listed in Table 7. MiR-200c induces apoptosis by targeting the expression of XIAP [126].…”

“…Liu et al reported that miR-4458 inhibited the cell proliferation and promoted cell apoptosis through negatively regulating the expression of suppressor of cytokine signaling 1 (SOCS1) [174]. Moreover, miR-890 inhibits cell proliferation and invasion, inducing apoptosis by negatively regulating its target gene CD147 in TNBC cells [175], and Zhang et al showed that overexpression of miR-509 increased apoptosis and inhibited invasion probably by suppressing tumor necrosis factor-α (TNF-α) in TNBC cells [176]. Additionally, there are other panels of miRNAs with tumor suppressor properties involved in TNBC.…”