<p>GATA1 gene silencing inhibits invasion, proliferation and migration of cholangiocarcinoma stem cells via disrupting the PI3K/AKT pathway</p>
Authors: Qiong Yu
Hong Zhang
Guang Shi
Youbo Ji
Chunmei Hu
Journal: OncoTargets and Therapy (2019)
Discipline: CLINICAL MEDICINE
Keywords: GATA1; PI3K/AKT pathway; cholangiocarcinoma stem cells; gene silencing; invasion
Affiliations: Department of Hematology and Oncology, the Second Hospital of Jilin University, Changchun 130041, People's Republic of China., Department of Clinical Medicine, Changchun Medical College, Changchun 130031, People's Republic of China., Department of Pain, the Second Hospital of Jilin University, Changchun 130041, People's Republic of China.

Abstract:  Background/aims: Intrahepatic cholangiocarcinoma (CCA) is the second most prevalent type primary liver malignancy, accompanied by an increasing global incidence and mortality rate. Research has documented the contribution of the GATA binding protein-1 (GATA1) in the progression of liver cancer. Here, we aim to investigate the role of GATA1 in CCA stem cells via the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) pathway. Methods: Initially, microarray-based gene expression profiling was employed to identify the differentially expressed genes associated with CCA. Subsequently, an investigation was conducted to explore the potential biological significance behind the silencing of GATA1 and the regulatory mechanism between GATA1 and PI3K/AKT pathway. CCA cell lines QBC-939 and RBE were selected and treated with siRNA against GATA1 or/and a PI3K/AKT pathway inhibitor LY294002. In vivo experiment was also conducted to confirm in vitro findings. Results: GATA1 exhibited higher expression in CCA samples and was predicted to affect the progression of CCA through blockade of the PI3K/AKT pathway. siRNA-mediated downregulation of GATA1 and LY294002 treatment resulted in reduced proliferation, migration and invasion abilities of CCA stem cells, together with impeded tumor growth, and led to increased cell apoptosis and primary cilium expression. Additionally, the siRNA-mediated GATA1 downregulation had an inhibitory effect on the PI3K/AKT pathway. LY294002 was manifested to enhance the inhibitory effects of GATA1 inhibition on CCA progression. These in vitro findings were reproduced in vivo on siRNA against GATA1 or LY294002 injected nude mice. Conclusion: Altogether, the present study highlighted that downregulation of GATA1 via blockade of the PI3K/AKT pathway could inhibit the CCA stem cell proliferation, migration and invasion, and tumor growth, and promote cell apoptosis, primary cilium expression. 

Retracted: Yes

PubPeer comments:
 Shi G, Zhang H, Yu Q, Hu C, Ji Y. Onco Targets Ther. 2019;12:5335u2014 5354. The Editor and Publisher of OncoTargets and Therapy wish to retract the published article. The journal was notified of potential image manipulation in Figure 4D: u25cf Figure 4D 0 h panel GATA1 appears to show partial duplication with Figure 4D 0 h panel si-GATA1. u25cf Figure 4D 0 h si-GATA appears to show partial duplication with Figure 4D 0 h panel LY294002. The authors could not provide the satisfactory raw data for the study and the Editor has determined the findings are no longer valid and requested for the paper to be retracted. Our decision-making was informed by our policy on publishing ethics and integrity and the COPE guidelines on retraction. The retracted article will remain online to maintain the scholarly record, but it will be digitally watermarked on each page as u201cRetractedu201d. , 
 The retraction is useful, in that it links a distinctive style of Western Blots with the products of a papermill. ![file] ----------------- UPDATE: I made a montage of curious Western Blots, representing a distinct style. They are marked by high contrast and an absence of any background texture, and resemble ink blobs. They are not always sharp-edged; sometimes the ink appears to have spread, creating filaments. When there are double bands (ERK 1 2, JNK 1 2, LC3 I II, the sub-bands are somehow decoupled: differing in overall profile and in the width of the protein blobs, and with horizontal displacements, almost falling into different lanes. The papers that contain them tend to be problematic in other ways (some have been retracted). Their manifestations began in 2019 papers, and stopped in 2020 as if their use became deprecated. ![] Sources include - [He et al (2020)] - [Chang et al (2020)] - [Shang et al (2020)] - [Shi et al (2019)] *[RETRACTED]* - [Xu et al (2019)] *[RETRACTED]* - [Jia et al (2020)] - [Feng et al (2019)] Examples could be multiplied but I will settle for three more examples, to show the range of this gamut, from - [Qu et al (2019)] *[RETRACTED]* - [Song et al (2019)] *[RETRACTED]* - [Shi et al (2019)] . ![file] ,