Taken together, our findings demonstrate the critical role of miR-330-5p in promoting HCC progression via targeting SPRY2 to activate MAPK/ERK signaling, which may provide a novel and promising prognostic marker and therapeutic target for HCC.
SPRY1 expression was also found to be significantly up-regulated in the cases without underlying cirrhosis compared with those with cirrhosis (log fold change of 0.35 and -0.02, respectively, P < 0.05), whereas SPRY2 expression was significantly lower in the cases with advanced HCC (log fold change of -0.12 and -0.52 in early and advanced stages, respectively, P < 0.05) and in those with angiolymphatic invasion (log fold change of -0.47 and -0.16 in the presence and absence thereof, P < 0.05).
Multivariate analysis further established Spry2 as an independent predictor of postoperative recurrence in HCC patients (HR=1.47; 95% CI, 1.02-2.08; P=0.037).
The human HLE hepatocellular carcinoma (HCC) cell line, stably overexpressing AKT, was transfected with Spry2Y55F to study the molecular mechanisms underlying hepatocarcinogenesis driven by Spry2 loss.
Our study provides evidence that inhibition of Spry activity cooperates with other oncogenes to promote liver cancer in mouse models, and Spry2 may function as a candidate tumor suppressor for HCC development in vivo.
Our study provides evidence that inhibition of Spry activity cooperates with other oncogenes to promote liver cancer in mouse models, and Spry2 may function as a candidate tumor suppressor for HCC development in vivo.
Our study clearly indicates a role for Spry2 in hepatocellular carcinoma, and an understanding of the regulatory controls of its expression could provide new means of regulating the angiogenic switch in this hypervascular tumor, thereby potentially controlling tumor growth.
Our study clearly indicates a role for Spry2 in hepatocellular carcinoma, and an understanding of the regulatory controls of its expression could provide new means of regulating the angiogenic switch in this hypervascular tumor, thereby potentially controlling tumor growth.