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CXCL12 and MMP-9 expression may also be linked to miRNAs, an understudied class of small noncoding RNAs that are processed from RNA precursors by a set of ribonucleases that comprise Drosha–DGCR8 complex ([@bib12]). After being released to the extracellular space, miRNAs can act on various gene targets and participate in almost all biological processes. MiRNAs also function through the canonical function of mRNAs ([@bib16]; [@bib33]). However, miRNAs have been shown to regulate gene expression at the translational or protein expression level ([@bib45]). One of the ways that miRNAs control protein expression is by activating the MAPK pathway ([@bib23]). Another way is by inhibiting mTOR signaling ([@bib48]). CXCR4/CXCL12 axis is a clear example of the latter mechanism ([@bib14]). Meanwhile, mTOR kinase is a downstream effector of MAPK signaling ([@bib9]; [@bib40]). In our study, inhibition of MAPK suppressed both CXCL12 and MMP-9 expression. The activation of the PI3K/AKT pathway may also affect CXCL12/CXCR4 axis through modulating MAPK ([@bib48]). However, whether MAPK and AKT are in a common pathway that is involved in MMP-9 expression remains unclear.

One of the interesting findings in our study is that tumor-associated fibroblasts are a major contributor to MMP-9 expression in ccRCC. This is based on our observation that MMP-