RNAi mediated Tiam1 gene knockdown inhibits invasion of retinoblastoma
Authors: Rupinder K Kanwar
Subramanian Krishnakumar
Jagat R Kanwar
Saranya Navaneethakrishnan
Jyotirmay Biswas
Nithya Subramanian
Journal: PLoS ONE (2013)
Discipline: Multidisciplinary
Keywords: T lymphoma invasion and metastasis protein (Tiam1); cancer; metastasis; retinoblastoma (RB); invasiveness
Affiliations: Larsen and Toubro Department of Ocular Pathology, Vision Research Foundation, Sankara Nethralaya, Chennai, India

Abstract:  T lymphoma invasion and metastasis protein (Tiam1) is up-regulated in variety of cancers and its expression level is related to metastatic potential of the type of cancer. Earlier, Tiam1 was shown to be overexpressed in retinoblastoma (RB) and we hypothesized that it was involved in invasiveness of RB. This was tested by silencing Tiam1 in RB cell lines (Y79 and Weri-Rb1) using siRNA pool, targeting different regions of Tiam1 mRNA. The cDNA microarray of Tiam1 silenced cells showed gene regulations altered by Tiam1 were predominantly on the actin cytoskeleton interacting proteins, apoptotic initiators and tumorogenic potential targets. The silenced phenotype resulted in decreased growth and increased apoptosis with non-invasive characteristics. Transfection of full length and N-terminal truncated construct (C1199) clearly revealed membrane localization of Tiam1 and not in the case of C580 construct. F-actin staining showed the interaction of Tiam1 with actin in the membrane edges that leads to ruffling, and also imparts varying invasive potential to the cell. The results obtained from our study show for the first time that Tiam1 modulates the cell invasion, mediated by actin cytoskeleton remodeling in RB. 

Retracted: No

PubPeer comments:
 There are multiple instances of image duplication in this paper. See top right and top left of image 5B - they are same (red boxes in attached figure). In Figure 6A and 6B there are 2 instances of image duplication (see green and blue boxes). ![file] , 
 I shared the concerns reported above by Doratifera in #1 with the journal in October 2015, almost five years ago. Here were the concerns as I reported them to the journal. I found one more overlap in Figure 6A: Figure 5B: ![file] Figure 6AB: ![file] , 
 #2 Yes, you are correct. We apologize and we have submitted corrections , 
 May 26, 2021 Expression of concern: https: journals.plos.org plosone article?id=10.1371 journal.pone.0252495 It reads:  Following the publication of this article [1], concerns were raised regarding results presented in Figs 5, 6 and 8. [....] * In Fig 5B, the 0hr Y79 Untreated panel and the 0hr Scrambled siRNA panel appear similar. * The Y79 siTiam 1 treated panel of Fig 6A partially overlaps with the Weri-Rb1 siScrambled treated panel of Fig 6B. * The Y79 siScrambled treated panel of Fig 6A partially overlaps with the Weri-Rb1 untreated and siTiam 1 treated panels of Fig 6B. * The 0Hr-Y79 C1199 Tiam 1 panel of Fig 8A appears similar to the 0Hr-Weri-Rb1 Full length Tiam 1 panel of Fig 8B. The corresponding authors indicated that errors were made during the compilations of Figs 5 and 8 resulting in accidental duplications of the Fig 5B 0hr Y79 Untreated panel and the Fig 8B 0hr Weri-Rb1 Full length Tiam1 panel. Revised Figs 5 and 8 provided with this notice include updates to the Fig 5B 0hr Scrambled siRNA panel and the Fig 8A 0Hr-Y79 C1199 Tiam1 panel showing results from the original experiments. In addition, the corresponding authors explained that the partial overlap of panels presented in Fig 6 was the result of mixing files with similar names. A revised Fig 6 is provided to update the Y79 siTiam 1 treated, siScrambled treated, and Weri-Rb 1 siTiam1 treated panels showing results from the original experiment. The raw data underlying all other results reported in the article are available upon request from the corresponding authors. Updated Figs 5, 6 and 8 and their respective figure captions are provided here. A member of PLOS ONEu2019s Editorial Board advised that the updated figures support the results and conclusions reported in the original article. However, the PLOS ONE Editors issue this Expression of Concern due to the number of panels and figures affected and concerns regarding the overall reliability of the data presented in the original article. , 
 2021 expression of concern. https: journals.plos.org plosone article?id=10.1371 journal.pone.0252495 Following the publication of this article [1], concerns were raised regarding results presented in Figs 5, 6 and 8. Specifically, In Fig 5B, the 0hr Y79 Untreated panel and the 0hr Scrambled siRNA panel appear similar. The Y79 siTiam 1 treated panel of Fig 6A partially overlaps with the Weri-Rb1 siScrambled treated panel of Fig 6B. The Y79 siScrambled treated panel of Fig 6A partially overlaps with the Weri-Rb1 untreated and siTiam 1 treated panels of Fig 6B. The 0Hr-Y79 C1199 Tiam 1 panel of Fig 8A appears similar to the 0Hr-Weri-Rb1 Full length Tiam 1 panel of Fig 8B. The corresponding authors indicated that errors were made during the compilations of Figs 5 and 8 resulting in accidental duplications of the Fig 5B 0hr Y79 Untreated panel and the Fig 8B 0hr Weri-Rb1 Full length Tiam1 panel. Revised Figs 5 and 8 provided with this notice include updates to the Fig 5B 0hr Scrambled siRNA panel and the Fig 8A 0Hr-Y79 C1199 Tiam1 panel showing results from the original experiments. In addition, the corresponding authors explained that the partial overlap of panels presented in Fig 6 was the result of mixing files with similar names. A revised Fig 6 is provided to update the Y79 siTiam 1 treated, siScrambled treated, and Weri-Rb 1 siTiam1 treated panels showing results from the original experiment. The raw data underlying all other results reported in the article are available upon request from the corresponding authors. Updated Figs 5, 6 and 8 and their respective figure captions are provided here. A member of PLOS ONEu2019s Editorial Board advised that the updated figures support the results and conclusions reported in the original article. However, the PLOS ONE Editors issue this Expression of Concern due to the number of panels and figures affected and concerns regarding the overall reliability of the data presented in the original article. Reference 1.Subramanian N, Navaneethakrishnan S, Biswas J, Kanwar RK, Kanwar JR, Krishnakumar S (2013) RNAi Mediated Tiam1 Gene Knockdown Inhibits Invasion of Retinoblastoma. PLoS ONE 8(8): e70422. pmid:23950931 ,