miR663a-TTC22V1 axis inhibits colon cancer metastasis

An increasing number of studies have demonstrated that microRNAs (miRs) may act as oncogenes or anti-oncogenes in various types of cancer, including colon cancer (CC). However, the clinical and biological significance of miR663a in the prognosis of CC and its underlying molecular mechanisms remain unknown. Using the reverse transcription-quantitative polymerase chain reaction on CC and surgical margin tissue samples from 172 patients with CC, it was identified that miR663a was significantly downregulated in CC (P<0.001), particularly in metastatic CC (P=0.044). miR663a overexpression inhibited the proliferation and migration/invasion of CC cells in vitro, and also tumor growth and metastasis of CC cells in vivo. Additionally, miR663a target genes were analyzed. Inverse changes in tetratricopeptide repeat domain 22 variant 1 (TTC22V1) in response to alterations in miR663a expression were observed. miR663a decreased the reporter activity of the wild-type TTC22V1-3 untranslated region (UTR), but did not decrease that of a 3UTR mutant. miR663a completely abolished cell migration/invasion induced by TTC22V1 containing the wild-type 3UTR sequence, but not that induced by TTC22V1 containing the 3UTR mutant. An inverse correlation between miR663a and TTC22 mRNA levels was observed in CC tissues. These results suggest that TTC22V1 mRNA is a crucial miR663a target that directly promotes cell migration/invasion. TTC22, which, to the best of our knowledge, has rarely been investigated, is located in the nuclei of epithelial cells in colon stem cell niches at crypt bases, and is significantly downregulated in CC, particularly in non-metastatic CC. High TTC22V1 expression is a significant poor survival factor for patients with CC. Collectively, the results of the present study suggested that TTC22V1 may be a metastasis-associated gene and that the miR663a-TTC22V1 axis inhibited CC metastasis.