Aquaporin 3 maintains the stemness of CD133+ hepatocellular carcinoma cells by activating STAT3

Yawei Wang,Ye Yang,Qi Zhang,Shaolin Xu,Xueyan Fu,Gang Wu,Tianlong Wang

doi:10.1038/s41419-019-1712-0

Abstract

An increasing interest in liver cancer stemness arises owing to its aggressive behavior and poor prognosis. CD133, a widely known liver cancer stem cell marker, plays critical roles in the maintenance of liver cancer stemness. Thus, exploring the regulatory mechanism of CD133 expression is significant. In the present study, we proved the carcinogenesis roles of aquaporin 3 (AQP3) in hepatocellular carcinoma (HCC) and demonstrated that AQP3 promotes the stem cell-like properties of hepatoma cells by regulating CD133 expression. In addition, AQP3 promoted the stimulation and nuclear translocation of signal transducer and activator of transcription 3 (STAT3) with a subsequent increase in the level of CD133 promoter-acetylated histone H3. This phenomenon accelerated CD133 transcription. Next, whether AQP3 acted as an oncogenic gene in HCC and maintained the stemness of CD133+ hepatoma cells were elucidated; also, a novel mechanism underlying the AQP3/STAT3/CD133 pathway in HCC was deduced.

Highlights

Introduction InChina, hepatocellular carcinoma (HCC) is the fourth most commonly diagnosed and the third most prevalent cancer leading to an estimated 422,100 deaths annually[1]
We demonstrated that Aquaporin 3 (AQP3) functions as an oncogenic gene in HCC and maintains the stemness of CD133+ hepatoma cells
According to IHC in 120 HCC patients, AQP3 protein was found to be primarily expressed in the cytomembrane of the tumor cells (Fig. 1d)

Summary

Introduction

Introduction InChina, hepatocellular carcinoma (HCC) is the fourth most commonly diagnosed and the third most prevalent cancer leading to an estimated 422,100 deaths annually[1]. According to IHC in 120 HCC patients, AQP3 protein was found to be primarily expressed in the cytomembrane of the tumor cells (Fig. 1d). AQP3 expression was positively correlated with CD133 In order to explore the mechanism of AQP3 carcinogenesis, the mRNA expression profile of Lv-AQP3shRNA1-transfected HCCLM3 and HUH7 cells was compared with that of Lv-AQP3-NC transfected cells using a Human Tumor Proliferation/Invasion RT2 ProfilerTM PCR Array containing 86 cell proliferation/metastasis-related genes (Supporting files 1, 2).

Results

Conclusion