Abstract
Ultraconserved regions (UCRs) are non-protein-coding gene sequences that are strictly conserved across numerous distinct species. It has been demonstrated previously that UCRs encoding non-coding RNAs serve as regulators of gene expression. In recent decades, there has been increasing evidence for the involvement of UCRs in carcinogenesis. In previous studies, the non-coding RNA transcribed ultraconserved element 338 (TUC338) was identified to serve an oncogenic role in hepatocellular cancer; however, thus far, the role of TUC338 in cervical cancer (CC) remains undefined. The results of the present study revealed that TUC338 is significantly upregulated in CC tissues and cell lines, and that the upregulation of TUC338 is associated with lymph node metastasis. Transfection with small interfering RNA (siRNA) against TUC338 could markedly inhibit cell migration and invasion in HeLa and C33A CC cell lines. Using a dual-luciferase reporter assay, tissue inhibitor of metalloproteinase 1 (TIMP1) was demonstrated to be negatively regulated by TUC338 at the post-transcriptional level, via a specific target site within the 3' untranslated region. The expression of TIMP1 was also observed to be inversely associated with TUC338 expression in CC tissues. Overexpression of TIMP1 with MigRI-TIMP1-green fluorescent protein inhibited CC cell migration and invasion and downregulated matrix metalloproteinase 9, resembling the effects of TUC338 siRNA. Therefore, the results of the present study suggest that TUC338 acts as a novel oncogene by targeting the TIMP1 gene, and inhibiting CC cell migration and invasion.