Long noncoding RNA PVT1-214 promotes proliferation and invasion of colorectal cancer by stabilizing Lin28 and interacting with miR-128
Authors: Feng He
Jie Cao
Tong Zhang
Wanglin Li
Fei Wang
Jianchang Wei
Zhi Yang
Huacui Chen
Zhuanpeng Chen
Zhi Song
Ping Yang
Qiang Wang
Fang Wei
Journal: Oncogene (2019)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: lncRNAs; colorectal cancer; PVT1-214; Lin28; miR-128
Affiliations: Department of General Surgery, Guangzhou Digestive Disease Center, Guangzhou First People's Hospital, The Second Affiliated Hospital of South China University of Technology, Guangzhou, 510180, China., Department of Nephrology, Guangzhou First People's Hospital, The Second Affiliated Hospital of South China University of Technology, Guangzhou, 510180, China., Department of Pathology, Yale University School of Medicine, New Haven, 06520, CT, USA., Department of Operative Dentistry and Endodontics, Guanghua School of Stomatology, Hospital of Stomatology, Sun Yat-sen University and Guangdong Provincial Key Laboratory of Stomatology, Guangzhou, 510055, China., Department of General Surgery, Guangzhou First People's Hospital, Guangzhou Medical University, Guangzhou, 510180, China., Department of General Surgery, Guangzhou Digestive Disease Center, Guangzhou First People's Hospital, The Second Affiliated Hospital of South China University of Technology, Guangzhou, 510180, China. ., Department of General Surgery, Guangzhou First People's Hospital, Guangzhou Medical University, Guangzhou, 510180, China. .

Abstract:  Long noncoding RNAs (lncRNAs) are implicated in human cancer, but their mechanisms of action are largely unknown. In this study, we investigated lncRNA alterations that contribute to colorectal cancer (CRC) through microarray expression profiling in CRC patient samples. Here, we report that the CRC-associated lncRNA PVT1-214 is a key regulator of CRC development and progression; patients with high PVT1-214 expression had a shorter survival and poorer prognosis. In vitro and in vivo investigation of the role of PVT1-214 revealed a complex integrated phenotype affecting cell growth, stem-like properties, migration, and invasion. Furthermore, using RNA pull-down and mass spectrometry, we found that Lin28 (also known as Lin28A), a highly conserved RNA-binding protein, is associated with PVT1-214. Strikingly, we found that PVT1-214 not only upregulated Lin28 protein expression in CRC cells by stabilizing Lin28, but also participated in crosstalk with Lin28 mRNA through competition for miR-128 binding, imposing an additional level of post-transcriptional regulation. In addition, we further show that PVT1-214 repressed expression of let-7 family miRNAs, which was abrogated by Lin28 knockdown. Taken together, our findings support a model in which the PVT1-214/Lin28/let-7 axis serves as a critical regulator of CRC pathogenesis, which may simulate a new direction for CRC therapeutic development. 

Retracted: No

PubPeer comments:
 Figure 2h and 2j: A micrograph has been duplicated and presented as something else.  , 
 Figure 2h (Oncogene,2019) and Figure 4B (Oncotarget, 2016) A micrograph has been duplicated from an other paper published in 2016 by the same author . The same picture was used in two articles to describe different facts .  ,