MicroRNA-143 Targets Syndecan-1 to Repress Cell Growth in Melanoma
Authors: Jie Wang
Lizhou Jia
Yan Li
Lingli Zhang
Lidao Bao
Yan Duan
Ruiya Li
Na Sha
Journal: PLoS ONE (2014)
Discipline: Multidisciplinary
Keywords: Melanoma; microRNA-143; Syndecan-1; cell proliferation; tumor progression
Affiliations: Department of Dermatology, Inner Mongolia People's Hospital, Hohhot, Inner Mongolia Autonomous Region, China., Department of Pathology, Inner Mongolia People's Hospital, Hohhot, Inner Mongolia Autonomous Region, China., Department of Pathology, The Affiliated People's Hospital of Inner Mongolia Medical University, Hohhot, Inner Mongolia Autonomous Region, China., Department of Dermatology, The Affiliated Hospital of Inner Mongolia Medical University, Hohhot, Inner Mongolia Autonomous Region, China., Department of Pharmacy, The Affiliated Hospital of Inner Mongolia Medical University, Hohhot, Inner Mongolia Autonomous Region, China.

Abstract:  Melanoma is the most aggressive type of skin cancer with a rapid progression and a limited efficiency of therapeutics. Recently, studies have identified some microRNAs playing important roles in the development of melanoma. Syndecan-1 (Syn-1), dysregulated in many cancers, plays important roles in tumor progression by controlling cell proliferation. In this study, we investigated whether microRNA-143 (miR-143) is involved in the regulation of Syn-1 and thus plays a functional role in melanoma. We found that miR-143 expression was significantly lower in melanoma tissues than in normal tissues and its low expression was closely related to clinical stages of melanoma. Further experiments showed that consistent with the inhibitory effects induced by knockdown of Syn-1, overexpression of miR-143 suppressed cell proliferation, promoted G1 phase arrest and induced apoptosis in melanoma. Downregulation of miR-143 apparently produced opposite effects. Combined treatment of miR-143 overexpression and Syn-1 knockdown induced remarkable synergistic effects, while reconstitution of miR-143-resistant Syn-1 reversed the inhibitory activity of miR-143. Moreover, miR-143 level was inversely correlated with Syn-1 expression in melanoma cells. miR-143 directly targeted the 3'-untranslated regions of Syn-1 mRNA and they were in the same Argonaute2 complex. Taken together, this study revealed a link between miRNA-143 and Syn-1 in the pathogenesis of melanoma. MiR-143 plays an important role in the regulation of cell growth in melanoma. Restoration of miR-143 expression may represent a promising and efficient therapeutic approach for targeting malignant melanoma. 

Retracted: Yes

PubPeer comments:
 2018 retraction. https: journals.plos.org plosone article?id=10.1371 journal.pone.0205767 After publication of this article [1], concerns were raised about similarities between FACS plots shown in Figs 2E, 2F, and 5D: In Fig 2E and 2F, the pre-scramble, anti-scramble, and anti-miR-143 panels contain clusters of data points that appear similar. In Fig 2E and Fig 5D, the pre-scramble+NC siRNA, both pre-miR-143, and the Syn-1 siRNA panels contain clusters of data points that appear similar. We discussed these concerns with the authors who noted that the original data underlying these figures were no longer available. They provided supporting figures with apoptosis and proliferation data from different types of experiments but did not provide the raw data underlying the new results and were unable to clarify the issues about the published FACS data. We consulted members of PLOS ONE s Editorial Board about this article and about the new data provided post-publication. They advised that the published FACS plots showing similarities appear to have been derived from the same file using different gating parameters, and they further raised that experiments in the article used normal skin rather than isolated melanocytes as control samples to compare against melanoma samples, hence conclusions pertaining to melanoma were not supported. Overall, based on the advice we received, the concerns raised call into question the validity of the conclusions and whether they are sufficiently supported by the reported data. The authors did not respond to queries regarding the availability of raw data underlying the other results reported in the published article. In light of these concerns, the PLOS ONE Editors retract this article. The authors did not comment on the retraction decision. Reference 1. Li R, Zhang L, Jia L, Duan Y, Li Y, Wang J, et al. (2014) MicroRNA-143 Targets Syndecan-1 to Repress Cell Growth in Melanoma. PLoS ONE 9(4): e94855. https: doi.org 10.1371 journal.pone.0094855 pmid:24722758 , 
 An illustration of the similarities in the FACS plots of Figure 2E, 2F, and 5D. Boxes of the same color highlight areas that look similar to each other. ![file] ,