Upregulation of SNHG6 expression induced RKO and HCT116 cell proliferation as well as RKO cell metastasis, while downregulation of SNHG6 expression supressed the proliferation and metastasis of RKO cells and tumor growth <i>in vivo.</i> UPF1 was upregulated and ZEB1 was decreased when SNHG6 knockdown, regulating the TGF-β/Smad pathway and inducing EMT respectively.
Collectively, UPF1 functions as a tumor suppressor by preventing cancer stem cell (CSC)-like characteristics, inhibiting EMT process and enhancing chemotherapeutic sensitivity via inhibiting ABCC2 expression in HCC cells.
Additionally, the predominant nuclear localization of UPF1 in normal glandular cells and low grade tumors was switched to a more cytoplasmic pattern in carcinomas with Gleason score >7.
We show that NMD is responsible for this robust downregulation, as CDH1 transcripts harbouring PTCs in the KATO-III gastric tumour cell line were upregulated in response to protein synthesis inhibitors or depletion of the NMD factors UPF1 and eIF4AIII.