TRG-AS1 is a potent driver of oncogenicity of tongue squamous cell carcinoma through microRNA-543/Yes-associated protein 1 axis regulation
Authors: Shuwei He
Fan Zhou
Xu Wang
Jingjing Zhang
Lei Li
Xingmin Han
Journal: Cell Cycle (2020)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: anticancer therapies; ceRNA; lncRNAs.
Affiliations: Department of Nuclear Medicine, The First Affiliated Hospital of Zhengzhou University , Zhengzhou, Henan, P.R. China.

Abstract:  The long noncoding RNA T cell receptor gamma locus antisense RNA 1 (TRG-AS1) plays an important role in glioblastoma progression. The objective of this study was to determine the expression status of TRG-AS1 in tongue squamous cell carcinoma (TSCC). The regulatory effects of TRG-AS1 depletion on the malignant processes of TSCC cells were illustrated both in vitro and in vivo. Additionally, the precise molecular mechanisms through which TRG-AS promotes TSCC oncogenicity were investigated. TRG-AS1 expression in TSCC tissues and cell lines was detected using reverse transcription-quantitative PCR. Functional experiments including Cell Counting Kit-8 assay, flow cytometric apoptotic assay, migration and invasion assays, and xenograft tumor model analysis were conducted to severally determine the effects of TRG-AS1 on TSCC cell proliferation, apoptosis, migration, and invasion in vitro and tumor growth in vivo. Herein, TRG-AS1 was highly expressed in TSCC and closely associated with advanced TNM stage, high lymph node metastasis, and poor overall survival. Functionally, TRG-AS1 depletion suppressed TSCC cell proliferation, migration, and invasion in vitro; promoted cell apoptosis; and attenuated tumor growth in vivo. Mechanistically, TRG-AS1 served as a molecular sponge for microRNA-543 (miR-543), thereby contributing to the increased expression of Yes-associated protein 1 (YAP1) - a miR-543 target. Rescue experiments confirmed that miR-543 inhibition or YAP1 overexpression abrogated the anticancer effects of TRG-AS1 silencing in TSCC cells. In conclusion, TRG-AS1 aggravates TSCC malignancy by regulating the miR-543/YAP1 axis. Identification of the TRG-AS1/miR-543/YAP1 regulatory pathway may provide novel insights into TSCC diagnosis, prognosis, and therapy. 

Retracted: No

PubPeer comments:
 Two pairs of flow-cytometry plots seem to share most of their points in common, suggesting that both pairs are derived from single data sets. I have adjusted contrast and aspect ratios to facilitate comparison.   Both left-hand panels are from Figs 1f, 3c, 5c, 6c. Both right-hand panels are from Figs 1H, 2H, 4C, 5C of [Fan et al (2020)] .  -----------------------------------------------  There may be other matches, or matches with Figures from other papers in this oeuvre. , 
 Expression of Concern, [1 September 2021] . -------------------------------- After publication of this article, questions about the scientific integrity of the article content were brought to the Publisher and Editoru2019s attention. We have reached out to the authors requesting that they supply information that would confirm the articleu2019s integrity, but the authors have not responded to our queries within the requested timeframe. Therefore, as we continue to work through the issues raised, we advise readers to interpret the information presented in the article with due caution. The authors have been notified about this Expression of Concern. , 
 *[above]* Fig 7e f from  Long non-coding RNA GAS6-AS1 acts as a ceRNA for microRNA-585, thereby increasing EIF5A2 expression and facilitating hepatocellular carcinoma oncogenicity ([Ai et al 2020] ). *[lower left]* **Fig 5d**. *[lower right]* Fig 7G from  Long Noncoding RNA FOXD2-AS1 Promotes the Malignancy of Cervical Cancer by Sponging MicroRNA-760 and Upregulating Hepatoma-Derived Growth Factor ([Hou et al 2020]()).  , 
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 - *[left]* Fig 6E from  Long noncoding RNA VPS9D1-AS1 augments the malignant phenotype of non-small cell lung cancer by sponging microRNA-532-3p and thereby enhancing HMGA2 expression ([Han et al 2020] ). - *[right]* **Fig 5d**.  Fig 6E F from  MicroRNA-939 Directly Targets em HDGF em to Inhibit the Aggressiveness of Prostate Cancer via Deactivation of the WNT u03b2-Catenin Pathway ([Situ et al 2020] ) **[retracted]**.  , 
 - *[left]* Fig 5d again. - *[right]* Fig 5i from  Long noncoding RNA SNHG22 increases ZEB1 expression via competitive binding with microRNA-429 to promote the malignant development of papillary thyroid cancer ([Gao et al 2020] ) **[retracted]**.  , 
 - *[left]* Fig 6d from  Long Noncoding RNA KCNMB2-AS1 Increases ROCK1 Expression by Sponging microRNA-374a-3p to Facilitate the Progression of Nonu2013Small-Cell Lung Cancer ([Yang et al 2020] ). - *[right]* **Fig 5e**.  ,