The long coding RNA AFAP1-AS1 promotes tumor cell growth and invasion in pancreatic cancer through upregulating the IGF1R oncogene via sequestration of miR-133a
Authors: Wujun Xiong
Qiqi Zhang
Xujing Wang
Yongkun Wang
Xiaohua Jiang
Huiren Zhuang
Qinhua Li
Bo Chen
Yongping Zhou
Journal: Cell Cycle (2018)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: LncRNA AFAP1-AS1/miR-133a/IGF1R axies; Pancreatic cancer; competitive endogenous RNA (ceRNA).
Affiliations: Department of Hepatopancreatobiliary Surgery, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China, Department of Hepatology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China, Department of Hepatobiliary Surgery, Wuxi Second Hospital, Nanjing Medical University, Wuxi, Jiangsu, China, Department of Gastroenterological Surgery, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China

Abstract:  Long non-coding RNAs (lncRNAs) have been shown to play a significant role in the progression of many cancers, including pancreatic cancer (PC). However, the biological function and regulatory mechanisms of lncRNAs in PC remains largely unclear. The aim of this study was to identify and evaluate the potential functions of lncRNAs in PC and reveal the underlying mechanisms of their effects. Screening of published microarray data (GEO accession Nos. GSE16515 and GSE32688), revealed lncRNA AFAP1-AS1 to be one of the most upregulated lncRNAs in PC tissues. High expression of AFAP1-AS1 was correlated with advanced stages, tumor size and lymph node metastasis, as well as with poorer overall survival in patients with PC. Functionally, knockdown of AFAP1-AS1 by transfection with siRNA inhibited the proliferative and invasive capacities of PaCa-2 and SW1990 PC cells, promoted apoptosis of PC cells in vitro, and impaired in-vivo tumorigenicity. In particular, it was hypothesized that AFAP1-AS1 may act as a competitive endogenous RNA (ceRNA), effectively becoming a sink for miR-133a whose expression was found to be downregulated in PC tissues and cell lines, and which was negatively correlated with the expression of AFAP1-AS1. We also found that the IGF1R oncogene which is an important regulator of MEK/ERK signaling pathway, was positively regulated by AFAP1-AS1 through ameliorating miR-133a-mediated IGF1R repression in PC tissues. Moreover, we demonstrated that knockdown of IGF1R by transfection with si-IGF1R suppressed cell proliferation, invasion and migration of PaCa-2 and SW1990 PC cells, suggesting that IGF1R may function as an oncogene in PC cells. Further investigations revealed that miR-133a reversed the biological effects of AFAP1-AS1 on PC cells. Collectively, the findings provide new evidence that AFAP1-AS1 could regulate the progression of pancreatic cancer by acting as a ceRNA, and suggest it has potential for use as both a biomarker for the early detection PC and for the development of individualized therapies for PC. 

Retracted: No

PubPeer comments:
 Two studies, the same Ethic Comitee number : https: doi.org 10.3390 cancers13092169 and https: doi.org 10.3390 cancers13133335 The results of the two studies have significant overlaps. , 
 #1 Dear Colleague Thank you for your interest in our articles. It is obvious for anyone reading the two studies that these articles are originating from the same project on a large chordoma series. These two studies are impossible to publish in the same paper: the two works have different aims, with different antibodies methodology used to answer the questions, and of course with different results. Besides, we do mention three times in the first published article (10.3390 cancers13092169), the other work (still under submission at that time). Best regards Georgia Karpathiou Michel Pu00e9oc h ,