RNAi-mediated silencing of AQP1 expression inhibited the proliferation, invasion and tumorigenesis of osteosarcoma cells
CANCER BIOLOGY & THERAPY
Authors: Wu, Zhong; Li, Shaohua; Liu, Jie; Shi, Yongzhen; Wang, Jianguang; Chen, Dong; Luo, Linjie; Qian, Yongqiang; Huang, Xiang; Wang, Hua
Abstract
Aquaporin 1 (AQP1), a member of water channel proteins, functions as a water-selective transporting protein in cell membranes. In recent years, AQP1 has been found to be overexpressed in various tumors. However, the molecular mechanism underlying the biological function of AQP1 in osteosarcoma is still unclear. This study was aimed at elucidating the roles of AQP1 in regulating the biological behavior of osteosarcoma cells. In this study, we found that AQP1 mRNA was elevated in osteosarcoma tissue. High level of AQP1 was associated with poor prognosis in osteosarcoma. Then, we found that knockdown of AQP1 in osteosarcoma cells, U2OS or MG63 cells inhibited cell proliferation and significantly increased cells population in G1 phase. Additionally, suppressing AQP1 expression in osteosarcoma cells dramatically induced cell apoptosis. We also found that down-regulation of AQP1 significantly inhibited cell adhesion and invasion. More importantly, AQP1 knockdown inhibited tumor growth in vivo and prolonged the survival time of nude mice. Gene set enrichment analysis (GSEA) showed that transforming growth factor-beta ( TGF-beta) signaling pathway and focal adhesion genes was correlatively with AQP1 expression. In addition, real time PCR and western blot analysis revealed that expression of TGF-beta 1/TGF-beta 2, RhoA and laminin beta 2 (LAMB2) was remarkably impaired by AQP1 silencing. In conclusion, AQP1 may be a useful diagnosis and prognosis marker for osteosarcoma. AQP1 knockdown can effectively inhibit cell proliferation, adhesion, invasion and tumorigenesis by targeting TGF-beta signaling pathway and focal adhesion genes, which may serve a promising therapeutic strategy for osteosarcoma.
High Expression of Three-Gene Signature Improves Prediction of Relapse-Free Survival in Estrogen Receptor-Positive and Node-Positive Breast Tumors
BIOMARKER INSIGHTS
Authors: Thakkar, Arvind; Raj, Hemanth; Ravishankar; Muthuvelan, Bhaskaran; Balakrishnan, Arun; Padigaru, Muralidhara
Abstract
The objective of the present study was to validate prognostic gene signature for estrogen receptor alpha-positive (ER alpha+) and lymph node (+) breast cancer for improved selection of patients for adjuvant therapy. In our previous study, we identified a group of seven genes (GATA3, NTN4, SLC7A8, ENPP1, MLPH, LAMB2, and PLAT) that show elevated messenger RNA (mRNA) expression levels in ER alpha (+) breast cancer patient samples. The prognostic values of these genes were evaluated using gene expression data from three public data sets of breast cancer patients (n=395). Analysis of ER alpha (+) breast cancer cohort (n=195) showed high expression of GATA3, NTN4, and MLPH genes significantly associated with longer relapse-free survival (RFS). Next cohort of ER alpha (+) and node (+) samples (n=109) revealed high mRNA expression of GATA3, SLC7A8, and MLPH significantly associated with longer RFS. Multivariate analysis of combined three-gene signature for ER alpha (+) cohort, and ER alpha (+) and node (+) cohorts showed better hazard ratio than individual genes. The validated three-gene signature sets for ER alpha (+) cohort, and ER alpha (+) and node (+) cohort may have potential clinical utility since they demonstrated predictive and prognostic ability in three independent public data sets.