Background
Clear cell renal cell carcinoma (ccRCC) is identified as a malignant tumor in the urinary tract. The research was an attempt to probe the biological function and molecular mechanism of lncRNA LINC00667 in ccRCC development.
Conclusions
LINC00667 is up-regulated in ccRCC and enhances the ZEB1 expression by targeting miR-143-3p, which in turn accelerates ccRCC progression and induces chemoresistance.
Methods
qRT-PCR monitored LINC00667, miR-143-3p, and ZEB1 levels. The models of LINC00667, miR-143-3p, and ZEB1 overexpression or knockdown were constructed in ccRCC cells. Cell proliferation, apoptosis, migration, and invasion of the cells were detected. The levels of apoptosis-associated proteins and epithelial-mesenchymal transition (EMT)-related proteins, and ZEB1 were detected by WB. Dual-luciferase reporter assay and RNA pull-down assay identified the binding association between LINC00667 and miR-143-3p, miR-143-3p and ZEB1. Moreover, a xenograft tumor model in nude mice was used for evaluating tumor growth in vivo.
Results
LINC00667 and ZEB1 displayed high expression in ccRCC tissues and cells. miR-143-3p was lowly expressed in ccRCC tissues and cells. LINC00667 targeted and repressed miR-143-3p, which inhibited ZEB1 expression in a targeted manner. Overexpression of LINC00667 facilitated ccRCC cell proliferation, migration, invasion and EMT and retarded apoptosis, whereas LINC00667 knockdown or miR-143-3p overexpression exerted reverse effects. The rescue experiments indicated that overexpressing miR-143-3p dampened LINC00667-mediated oncogenic effects. Overexpressing ZEB1 diminished miR-143-3p-mediated tumor-suppressive effects. In-vivo experiments displayed that overexpression of LINC00667 contributed to the tumor growth of ccRCC cells, in contrast to miR-143-3p overexpression, which restrained the tumor growth. Conclusions: LINC00667 is up-regulated in ccRCC and enhances the ZEB1 expression by targeting miR-143-3p, which in turn accelerates ccRCC progression and induces chemoresistance.