[No authors listed]
Long nonâcoding (lnc)RNA sprouty receptor tyrosine kinase signalling antagonist 4âintronic transcript 1 (SPRY4âIT1) has been demonstrated to serve a critical role in the tumorigenesis of osteosarcoma (OS); however, the specific underlying mechanism remains unclear. The aim of the present study was to examine the interactions between SPRY4âIT1 and its downstream effectors, to determine if any of the interactions contributed to SPRY4âIT1âmediated proliferation, migration and invasion in cancer cells. A signalling cascade which involved SPRY4âIT1, miRâ101 and zinc finger Eâboxâbinding homeoboxes (ZEBs) was examined in the present study. Intracellular SPRY4âIT1 and miRâ101 expression levels were altered through transfection to assess their effect on proliferation, cell cycle progression, survival, migration and invasion. A dualâluciferase assay was utilized to determine the association between SPRY4âIT1/miRâ101 and ZEBs/miRâ101 and nude mouse xenograft experiments were performed to determine the effect of SPRY4âIT1 in vivo. The results indicated that the SPRY4âIT1 levels were negatively associated with miRâ101 expression levels in OS cells, an association which was not observed in the normal osteoblast cells. SPRY4âIT1 knockdown or miRâ101 overexpression reduced proliferation, cell cycle progression, survival, migration and invasion of MGâ63 and U2OS cells. SPRY4âIT1 knockdown was accompanied by increased expression of miRâ101 and Eâcadherin levels, as well as decreased expression levels of ZEB1/2 and other epithelialâmesenchymal transitionâassociated proteins. Simultaneous knockdown of SPRY4âIT1 and inhibition of miRâ101 partially reversed the antiâtumour effects of SPRY4âIT1 inhibition in vitro. Consistent with these findings, short hairpin RNA targeting SPRY4âIT1 also hindered xenograft tumour growth and altered the levels of miRâ101, ZEB1/2 and Eâcadherin in vivo. Dualâluciferase reporter assays demonstrated that SPRY4âIT1 may have regulated the expression of ZEB1 and ZEB2 by sponging miRâ101. In conclusion, SPRY4âIT1 inhibition increased miRâ101 levels, resulting in downregulation of ZEB1/2 expression and thus exerting antiâtumour effects in OS.
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 }} |