CASC2 overexpression suppressed the cell proliferation and promoted apoptosis in PTC cell lines and CASC2 overexpression resulted in the inactivation of protein kinase B (PKB/AKT) and extracellular signal-regulated kinases (ERK1/2).
Expression of HOTTIP, miR-637 and Akt1 were determined by quantitative RT-PCR (qRT-PCR) and western blotting in PTC tissues, normal tissues, PTC cells (TPC-1 and HTH83) or non-tumor thyroid cells (Nthy-ori 3-1).
In studying the expression of phosphoinositide-3 kinase (PI3K)/RACserine/threonine-protein kinase (Akt) pathway, the upregulation of Ang1/Tie2 was found to be associated with the activation of the PI3K/Akt pathway in PTC.
To approach this question, we performed immunohistochemistry for phospho-AKT Ser473 (mTORC2 effector) in a series of 182 PTCs previously characterized for phospho-mTOR and phospho-S6 expression.
Overexpression of miRNA‑148a significantly induced Bax protein expression and caspase‑3/9 levels, and suppressed phosphorylation STAT3 (p‑STAT3), PI3K and p‑Akt protein expression of papillary thyroid cancer in vitro.
We show that active AKT has a predominantly nuclear distribution and its expression is highest in anaplastic thyroid carcinomas and papillary thyroid carcinomas, including encapsulated and invasive follicular variants.
In addition, we demonstrated that ectopic expression of miR-451a impairs proliferation and migration of two PTC-derived cell lines, reduces the protein levels of its recognized targets MIF, c-MYC and AKT1 and attenuates AKT/mTOR pathway activation.Overall, our study provide both an updated overview of miRNA deregulation in PTC and the first functional evidence that miR-451a exerts tumor suppressor functions in this neoplasia.
The results suggested that PIG3 plays an oncogenic role in PTC via the regulation of the PI3K/AKT/PTEN pathway and support the exploration of PIG3 as a novel biomarker for patients with PTC.
In addition, expression of Sin1 and activation of AKT kinase were analyzed in fresh-frozen tissue samples (normal/tumor), primary cell cultures (papillary thyroid carcinoma [PTC]), and an established thyroid cancer cell line (medullary thyroid carcinoma) by Western blotting.
Interestingly, coexpression of mTORC1 and mTORC2 activity was seen in a 32.5% (164/504) of the PTC studied and this association was statistically significant (P = 0.0244). mTOR signaling complex was also found to be associated with activated AKT and 4E-BP1.
The fact that most of the PTC cases that had activated AKT showed overexpression of c-MET (p = 0.027) leads us to hypothesize that c-MET may be an alternative mechanism of AKT activation in Middle Eastern PTCs.
In summary, these observations suggest that RET/PTC is able to phosphorylate the Y315 residue of PKB, an event that results in maximal activation of PKB for RET/PTC-induced thyroid tumorigenesis.