Long noncoding RNA LINC00657 enhances the malignancy of pancreatic ductal adenocarcinoma by acting as a competing endogenous RNA on microRNA-433 to increase PAK4 expression
Authors: Qingchang Li
Hu Feng
Yan Wang
Shasha Bi
Journal: Cell Cycle (2020)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: LINC00657; PAK4; microRNA-433; pancreatic ductal adenocarcinoma; target therapy.
Affiliations: Department of Pathology, College of Basic Medical Sciences, China Medical University, Shenyang, P.R.China., Department of Pathology, The First Affiliated Hospital of China Medical University, Shenyang, P.R.China., Department of General Oncotherapy, WeiHai Municipal Hospital, Shandong, P.R.China.

Abstract:  A long noncoding RNAs (lncRNA) called LINC00657 is dysregulated and contributes to tumor progression in a number of human cancer types. However, there is limited information on the expression profile and functions of LINC00657 in pancreatic ductal adenocarcinoma (PDAC). The expression profile of LINC00657 in PDAC was estimated by reverse-transcription quantitative polymerase chain reaction (RT-qPCR). The effects of LINC00657 upregulation on PDAC cell proliferation, apoptosis, migration, and invasion in vitro and tumor growth in vivo were explored using CCK-8, flow cytometry, Transwell migration and invasion assays, and a xenograft tumor formation experiment, respectively. The results revealed that LINC00657 was evidently upregulated in the PDAC tumors and cell lines. High LINC00657 expression significantly correlated with the pathological T stage, lymph node metastasis, and shorter overall survival. Functional analysis demonstrated that LINC00657 knockdown inhibited the proliferation, migration, and invasion while promoted the apoptosis of PDAC cells. In addition, LINC00657 knockdown markedly suppressed tumor growth of these cells in vivo. In terms of the mechanism, LINC00657 could directly interact with microRNA-433 (miR-433) and effectively worked as an miR-433 sponge, thus decreasing the competitive binding of miR-433 to PAK4 mRNA and ultimately increasing PAK4 expression. The actions of LINC00657 knockdown on malignant phenotype of PDAC cells were strongly attenuated by miR-433 inhibition and PAK4 restoration. These results indicate that LINC00657 promotes PDAC progression by increasing the output of the miR-433-PAK4 regulatory loop, thus highlighting the importance of the LINC00657-miR-433-PAK4 network in PDAC pathogenesis. 

Retracted: Yes

PubPeer comments:
 *[right]* Fig 7b.  Representative images of the [Panc-1] tumor xenografts from groups si-LINC00657 and si-NC . *[left]* Fig 7B from [Gao et al (2020)] .  Representative images of [TE-1] tumor xenografts obtained from the sh-FGD5-AS1 group and sh-NC group . Could either team of authors comment on the double publication of the image? ![file] , 
 Retracted [1 September 2021] . ------------------------------- Since publication, the authors informed us that ethical approval for the tumor xenograft experiments in mice reported in this article, had not been obtained from their institutional ethics committee. As this is a breach of research ethics requirements, the authors, Editor and Publisher have all agreed to retract the article to ensure the integrity of the scholarly record. We have been informed in our decision-making by our policy on publishing ethics and integrity and the COPE guidelines on retractions. The retracted article will remain online to maintain the scholarly record, but it will be digitally watermarked on each page as u2018Retractedu2019. , 
 - *[left]* Fig 2E from  MicroRNA-876 is sponged by long noncoding RNA LINC00707 and directly targets metadherin to inhibit breast cancer malignancy ([Li et al 2019] ). - *[right]* **Fig 2D**. ![file] Both papers are already retracted, but I think it is worth documenting the extent of figure reuse within the output of this papermill. ,