We discovered that: (1) differentially expressed (DE) mRNAs and DE miRNAs are potentially involved in SACC metastasis; (2) multiple regulatory interactions between DE miRNAs and DE mRNAs exist; and (3) miR-338-5p/3p target LAMC2 to impair motility and invasion of ACC-M and MDA-MB-231 cells.
ACC1 phosphorylation was mediated by TGFβ-activated kinase (TAK) 1, and ACC1 inhibition was indispensable for the elevation of cellular acetyl-CoA, the subsequent increase in Smad2 transcription factor acetylation and activation, and ultimately epithelial-mesenchymal transition and metastasis induction.
We found decreased effects on the proliferation phenotype of ACC-M cell in vivo and in vitro with XAGE-1b downregulation, and XAGE-1b overexpression promoted the proliferation of ACC-2 cells in vivo and in vitro, while its overexpression promoted the transmembrane invasion of ACC-2 cells in vitro and metastasis in vivo of the nude mice.
Despite its many drawbacks, mitotane continues to be a mainstay in the treatment of high-risk patients with ACC, especially those with recurrent or metastatic disease.
The two novel gene sequences have been named ACCmetastasis-associated RNH and ACCmetastasis-associated suspected protein (GenBank # AF522024 and AF522025, respectively).