Hypoxia-induced lncRNA CASC9 enhances glycolysis and the epithelial-mesenchymal transition of pancreatic cancer by a positive feedback loop with AKT/HIF-1α signaling
Authors: Han Han
Zhongchao Zhu
Pei Mei
Hanjun Li
Qiong Gong
Yuping Rong
Erhu Fang
Hehe Li
Yingyan Xiao
Jing Tao
Zhigang Tang
Zhengle Zhang
Journal: American journal of cancer research (2021)
Discipline: CLINICAL MEDICINE
Keywords: AKT; CASC9; EMT; HIF-1α; glycolysis
Affiliations: Department of Pancreatic Surgery, Renmin Hospital of Wuhan University Wuhan 430060, Hubei Province, China., Department of Pediatric Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology Wuhan 430022, Hubei Province, China., Department of Dermatology, Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology Wuhan 430014, Hubei Province, China., Department of Clinical Laboratory, Renmin Hospital of Wuhan University Wuhan 430060, Hubei Province, China., Department of Gastrointestinal Cancer Biology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy Tianjin 300060, China.

Abstract:  Increasing evidence indicates the dysregulations and pivotal roles of lncRNAs in the development and progression of various cancers, including pancreatic cancer. Enhanced glycolytic flux and epithelial-to-mesenchymal transition (EMT) have been considered as important factors in driving the malignance of pancreatic cancer. Here, we sought to evaluate the biological role and involved mechanism of lncRNA CASC9 (CASC9) in pancreatic cancer. Our present study showed that CASC9 was upregulated in various pancreatic cancer cell lines. Loss- and gain-of function of CASC9 demonstrated its critical roles in promoting the glycolysis and EMT phenotypes of pancreatic cancer. Moreover, knockdown of CASC9 inhibited the tumorigenicity and metastasis in vivo. Additionally, our findings showed that hypoxia induced the expression of CASC9 and enhanced the binding of HIF-1α to its promoter. We also demonstrated that the positive feedback loop of CASC9 and the AKT/HIF-1α signaling cascade partially mediated this biological process. Altogether, our results suggest that CASC9 promotes the glycolysis and EMT of pancreatic cancer by a positive feedback loop with AKT/HIF-1α signaling, which is synergistically enhanced by the tumor hypoxic niche. Our study will provide potential therapeutic targets for treating pancreatic cancer. 

Retracted: Yes

PubPeer comments:
 Retracted [15 June 2021] . --------------------------- In this article, we have included Dr. Zhongchao Zhu as one co-author in the published paper entitled u201cHypoxia-induced lncRNA CASC9 enhances glycolysis and the epithelial-mesenchymal transition of pancreatic cancer by a positive feedback loop with AKT HIF-1u03b1 signaling (Am J Cancer Res 2021;11:123-137)u201d. Actually, he didnu2019t make any contribution. Due to unclear of the study, he raised serious concern about the publication. We deeply regret what we have done. However, for the scientific rigor of study, we decided to retract the paper. We sincerely apologized for all the staffs involved this paper, including the editors, reviewers, and readers. Please contact me if you have any questions. ,