[No authors listed]
We previously reported that cystatin B (CSTB) is a progression marker of human ovarian cancer (OC); however, the regulatory mechanism of CSTB and its function in OC remain unclear. The present study aimed to explore the mechanism underlying transforming growth factor-β (TGFâβ) 1âmediated CSTB regulation, and to examine the function of CSTB on OC cell proliferation and apoptosis. Using the online program, miRWalk, a microRNA (miR)â143â3p was detected, which contains a homologous sequence of the potential binding site to the 3'âuntranslated region (3'âUTR) of CSTB. A dualâluciferase reporter assay confirmed the interaction between miRâ143â3p and CSTB 3'âUTR. Treating OC cells with miRâ143â3p mimics or inhibitors resulted in a decrease or an increase of CSTB expression at mRNA and protein levels, respectively. Additionally, CSTB was significantly overexpressed, whereas miRâ143â3p was downregulated in human OC tissues compared with normal ovarian tissues. A negative correlation between miRâ143â3p and CSTB mRNA expression was observed in ovarian malignant tumors. The levels of primary and mature miRâ143â3p expression were upregulated in OC cells after TGFâβ1 treatment; the action of TGFâβ1 was abolished in the presence of an inhibitor of TGFâβ type I receptor. These results indicated an axis between TGFâβ, miRâ143â3p and CSTB in OC cells. Furthermore, high levels of CSTB expression were associated with the poor overall survival of patients with OC. Knockdown of CSTB resulted in a decrease in OC cell proliferation and arrested cells in G2/M phase. In addition, suppression of CSTB induced cell apoptosis. In conclusion, CSTB was overexpressed and miRâ143â3p was downregulated in ovarian malignant tumors. Mature miRâ143â3p directly bound CSTB 3'âUTR, leading to a decrease in CSTB expression in OC cells, which was regulated by TGFâβ1. Our findings suggest the potential therapeutic application of targeting the TGFâβ/miRâ143â3p/CSTB axis for treating patients with OC.
KEYWORDS: {{ getKeywords(articleDetailText.words) }}
Sample name | Organism | Experiment title | Sample type | Library instrument | Attributes | |||||||||||||||||||||||||||||||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
{{attr}} | ||||||||||||||||||||||||||||||||||||||||||||||||||||||
{{ dataList.sampleTitle }} | {{ dataList.organism }} | {{ dataList.expermentTitle }} | {{ dataList.sampleType }} | {{ dataList.libraryInstrument }} | {{ showAttributeName(index,attr,dataList.attributes) }} |
{{ list.authorName }} {{ list.authorName }} |