406961

MIR185

STIM1 (stromal interaction molecule 1), an endoplasmic reticulum Ca(2+) sensor that triggers the store-operated Ca(2+) entry activation, has recently been implicated in cancer progression. However, the role of STIM1 in the progression and metastasis of colorectal cancer (CRC) has not been addressed. In this study, we confirmed increased expression of STIM1 in highly invasive CRC cell lines. Enhanced expression of STIM1 promoted CRC cell metastasis in vitro and in vivo, whereas silencing of STIM1 with small interfering RNA resulted in reduced metastasis. Ectopic expression of STIM1 in CRC cells induced epithelial-to-mesenchymal transition (EMT), whereas silencing of STIM1 had the opposite effect. Furthermore, STIM1 expression was markedly higher in CRC tissues than in adjacent noncancerous tissues. STIM1 overexpression correlated with poor differentiation and higher tumor node metastasis stage. CRC patients with positive STIM1 expression had poorer prognoses than those with negative STIM1 expression. Moreover, STIM1 was found to be a direct target of miR-185, a microRNA (miRNA) that has not previously been reported to be involved in EMT, in both CRC tissues and cell lines. Taken together, these findings demonstrate for the first time that STIM1 promotes metastasis and is associated with cancer progression and poor prognosis in patients with CRC. In addition, we show that expression of STIM1 is regulated by a posttranscriptional regulatory mechanism mediated by a new EMT-related miRNA. This novel miR-185-STIM1 axis promotes CRC metastasis and may be a candidate biomarker for prognosis and a target for new therapies.

In our previous study, advanced glycosylation endproduct specific receptor (RAGE) was observed to bind to S100A8/A9 and cause epithelial mesenchymal transition (EMT). The results from target gene prediction revealed that microRNA (miR)1855p had a RAGE binding site. However, the function of miR1855p in the invasion and migration of breast cancer remains ambiguous. In the present study, the expression of miR1855p was examined in breast cancer tissues and cells. Clinical features revealed a negative correlation between miR1855p and tumor size, as well as in tumor differentiation and lymph node metastasis in breast cancer. In addition, miR1855p was negatively associated with RAGE, and this miRNA reversed the EMT of breast cancer by modulating RAGE in vitro. In addition, miR1855p inhibited the S100A8/A9induced EMT of breast cancer cells by the nuclear factorkappaB/Snail signaling pathway. Notably, miR1855p upregulation inhibited the Factin polymerization induced by S100A8/A9 in breast cancer. Furthermore, overexpression of miR1855p and reduction of RAGE inhibited lung metastasis node in vivo. Thus, miR1855p represents a potential therapeutic target in breast cancer by modulating RAGE.

Melanoma is an aggressive skin carcinoma with poor prognosis. Increasing studies have been carried out to investigate effective therapeutic targets for melanoma treatment. This study focuses on the LncRNA UCA1 and its downstream regulated factors. In our present study, UCA1 expression was discovered to be up-regulated while miR-185-5p expression was down-regulated in melanoma tissues and cell lines. We found that miR-185-5p could directly bind to UCA1 at the miRNA recognition site, and there existed a negative relationship between UCA1 and miR-185-5p. Additionally, knockdown of UCA1 was found to suppress cell invasion through inhibiting EMT in melanoma. However, miR-185-5p inhibitor transfection counteracted the inhibitory effect of UCA1 shRNA on cell invasion and EMT, suggesting that UCA1 shRNA suppressed invasion through inhibiting EMT via up-regulating miR-185-5p expression in melanoma. In addition, depletion of UCA1 decreased the expression of beta-catenin and c-myc, indicating that UCA1 shRNA suppressed Wnt/beta-catenin signaling pathway. Moreover, activation of Wnt/beta-catenin signaling pathway by Licl treatment could abolish the effects of UCA1 shRNA on melanoma cells mobility and EMT. Finally, in vivo experiments revealed that knockdown of UCA1 inhibited tumor growth and invasion via targeting miR-185-5p through Wnt/beta-catenin signaling pathway. In conclusion, our study indicated that the UCA1/miR-185-5p/Wnt/beta-catenin axis might provide a new potential therapeutic strategy for melanoma treatment.CI - Copyright (c) 2018 Elsevier B.V. All rights reserved.