Data from: Axl-regulating tumor suppressor miR-34a increased in ccRCC but not correlating with Axl mRNA or Axl protein levels

Background: High expression of the receptor tyrosine kinase Axl is
associated with poor prognosis in patients with Renal Cell Carcinoma
(RCC), the most common malignancy of the kidney. The miR-34a has been
shown to directly regulate Axl in cancer cells. The miR-34a is a mediator
of p53-dependent tumor suppression, and low expression of miR-34a has been
associated with worse prognosis in several cancers. Our aim was to
elucidate whether miR-34a or the other members of the miR-34 family
(miR-34b/c) regulate Axl in RCC. Methodology and Results: Using western
blot, flow cytometry, and RT-qPCR, we showed that Axl mRNA and protein are
downregulated in 786-O cells by miR-34a and miR-34c but not by miR-34b. A
luciferase reporter assay demonstrated direct interaction between the Axl
3’ UTR and miR-34a and miR-34c. The levels of miR-34a/b/c were measured in
tumor tissue in a cohort of 198 RCC patients, and the levels of miR-34a
were found to be upregulated in clear cell RCC (ccRCC) tumors, but not
associated with patient outcome. Neither of the miR-34 family members
correlated with Axl mRNA, soluble Axl protein in serum, nor with
immunohistochemistry of Axl in tumor tissue. In addition, we measured mRNA
levels of a known miR-34a target, HNF4A, and found the HNF4A levels to be
decreased in ccRCC tumors, but unexpectedly correlated positively rather
than negatively with miR-34a. Conclusions: Although miR-34a and miR-34c
can regulate Axl expression in vitro, our data indicates that the miR-34
family members are not the primary regulators of Axl expression in RCC.