Lacking of treatment methods for the patients with triple negative breast cancer (TNBC) underscores the pivotal needs to further understand its biology as well as to find better biomarkers and develop novel therapeutic strategies. Increasing evidences support that aberrantly expressed microRNAs (miRNAs) are involved in tumorigenesis and may serve as biomarkers for diagnostic and prognostic purposes of various cancers. In current study, we found that miR-455-3p and miR-196a-5p were intensively overexpressed in TNBC compared with the hormone receptor (HR) positive breast cancer whereas miR-425-5p was down-regulated by miRNA microarray analysis. qRT-PCR analysis confirmed that the expression of miR-455-3p in TNBC cell lines MDA-MB-231 and MDA-MB-468 was higher than that in HR positive breast cancer cell line MCF-7(p<0.01). Functional experiments in vitro showed that miR-455-3p enhanced cell proliferative, invasive and migrational abilities in TNBC cell lines. miRNA targets prediction showed SMAD2, LTBR and etoposide induced 2.4 (EI24) were potential target genes of miR-455-3p, and then it was confirmed by qRT-PCR assay. Dual luciferase reporter assay showed the specific binding of miR-455-3p to 3′ UTR of EI24 in TNBC. Then we found miR-455-3p inhibited the EI24 expression at the levels of mRNA and protein. Through small interfering RNA (siRNA) targeting EI24 gene, there were strengthened capabilities of invasion and migration of TNBC cells, and increased expression of EI24 had the inverse effects. In conclusion, the data suggest that miRNA455-3p promotes invasion and migration by targeting tumor suppressor EI24 and might be a potential prognostic biomarker and therapeutic target in TNBC.

Invasive breast cancer is the most common type of malignancy in women worldwide. However, the mechanism responsible for breast cancer metastasis is still unclear and needs further illustration. It has been proven that matrix metallopeptidase 9 (MMP-9) promotes metastasis of the cancer cells. However, the interaction between mPRα and MMP-9 has not been studied. Therefore, in the present research, the effect of MMP-9 on the malignant progression of invasive breast cancer promoted by membrane progesterone receptorα (mPRα) was investigated. The results showed that the protein expression of mPRα, p-Akt and MMP-9 increased in the cancerous tissues compared to that of the noncancerous breast tissue. Furthermore, a positive correlation was found between mPRα and C-erbB-2, as well as the number of involved local lymph nodes. On the other hand, a negative correlation was observed between mPRα and estrogen receptors (ER) along with progesterone receptors (PR). Similarly, a positive association was found between MMP-9 and the number of involved local lymph nodes. Besides, the high expression of MMP-9 also had a positive correlation with the tumor size. However, the high level of MMP-9 had a negative correlation with ER and PR. In addition, there was a positive correlation between mPRα and p-Akt together with MMP-9. The results confirm that mPRα was a major marker of harmful prognosis and it promoted the expression of MMP-9 during invasion to the local lymph nodes through the pathway of PI3K/Akt. The present study provided a novel therapeutic strategy to inhibit breast cancer growth by preventing mPRα signaling pathway.

Background: Trichorhinophalangeal syndrome 1 (Trps1) gene is a member of GATA transcription factor family and has an important function in tumorigenesis and progression. However, there are rare studies on its roles in carcinogenesis and prognostic significance in human osteosarcoma. Methods: The expression of Trps1 was detected by immunohistochemistry, and MVD was evaluated to determine the amounts of microvessels by counting CD31-positive endothelial cells. Results: Of the 74 cases that underwent study, Trps1-positive cases were 24. And it was associated with MVD significantly (P = 0.008). The data also exhibited more cases of remote metastasis (P = 0.013) and higher Enneking stage (P = 0.017) in Trps1-positive group compared to Trps1-negative group. Univariate analysis revealed that distant metastasis, MVD and Trps1 expression were associated with a lower 3-year overall survival rate and disease-free survival rate (P = 0.003, and P = 0.012 respectively). Furthermore, Trps1 and distant metastasis retained their significant prognostic effects on patients survival rate by multivariate analysis (P < 0.05). Conclusions: Trps1 plays a crucial role in osteosarcoma angiogenesis, metastasis and clinical surgical stage. Trps1 can be a novel promising prognostic marker and therapeutic target, and antiangiogenic therapy which targets Trps1 molecule in patients with osteosarcoma may lead to improved prognosis and longer-term survival.