Expression and regulation of mTOR, a key modulator of ageing and age-related disease, in pancreatic carcinoma

Einleitung:

The mechanistic target of rapamycin (mTor) is known as a key modulator of ageing and age-related disease.

Ziele:

The aim of the present study was to investigate the mRNA and protein expression profile and clinical significance of mTOR in pancreatic cancer (PCA), pancreatic adenoma (PA) and pancreatitis patients as well as its miRNA operated regulation. As microRNAs (miRNAs) are naturally occurring non-coding regulatory molecules and key control elements of crucial regulatory pathways, we aimed to identify a specific miRNA regulating mTOR in pancreatic carcinoma.

Methodik:

MTOR expression was studied in affected and healthy neighboring tissue from patients with PCA (n = 22, respectively), PA (n = 8, respectively) and pancreatitis (n = 9, respectively) applying qRT PCR and immunohistochemistry (IHC). Various computer software programmes were employed to identify a specific miRNA that potentially interacts with mTor. Functional implications of miRNAs with the 3'UTR of mTor were analyzed by a Luciferase assay system.

Ergebnisse:

mTOR expression was significantly up-regulated in cancer tissue of PCA patients with respect to the healthy neighboring tissue (P < 0.05). Hence, a specific miRNA (miRNA-496) was identified by target prediction programmes to potentially interact with mTOR and subsequently demonstrated to functionally interact with mTOR. Thus, addition of the miRNA-496 led to significant down-regulation of luciferase activity (P < 0.05).

Schlussfolgerung:

We have demonstrated an aberrant expression profile of mTOR in PCA indicating that mTOR expression may play a specific role in PCA.