The inhibitory effect of MEG3/miR-214/AIFM2 axis on the growth of T-cell lymphoblastic lymphoma
Authors: Yan Zeng
Guang-Cui He
Fang-Yi Fan
Hao-Ping Sun
Yi Su
Rui Deng
Hai Yi
Journal: International Journal of Oncology (2017)
Discipline: CLINICAL MEDICINE
Keywords: T-cell lymphoblastic lymphoma; long non-coding RNA; MEG3; tumor suppressor; miRNA
Affiliations: Department of Hematology and Hematopoietic Stem Cell Transplantation and Cell Immunotherapy Center, Chengdu Military General Hospital of PLA, Chengdu, Sichuan 610083, P.R. China.

Abstract:  T-cell lymphoblastic lymphoma (T-LBL) is an aggressive malignancy with poor prognosis and high recurrence rate. Long non-coding RNA (lncRNA)-MEG3 is an important tumor suppressor in various cancers. The present study investigated the potential role of maternally expressed gene 3 (MEG3) in the progression of T-LBL. Suppressed expression of MEG3 was detected in T-LBL tissues compared with adjacent histologically normal tissues. Down-regulated level of MEG3 was also found in three T-LBL cell lines (CCRF-CEM, Jurkat and SUP-T1) compared with human T-cell line H9. The proliferation of T-LBL cells was inhibited and cell apoptosis rate was largely promoted when MEG3 was upregulated by a lentiviral vector. Further research revealed that microRNA (miRNA)-214 is a direct target of MEG3. The expression of miR-214 was increased in T-LBL tissues and cell lines compared with control groups. Besides, decreased level of miR-214 was elevated adding miR-214 mimic in SUP-T1 cells transfected with LncRNA-MEG3. Similarly, upregulated level of miR-214 was downregulated adding miR-214 inhibitor in SUP-T1 cells transfected with MEG3 siRNA. Luciferase activity assay further confirmed the targeting relationship between MEG3 and miR-214. Moreover, AIFM2 protein was predicted as a target of miR-214. The expression of AIFM2 was increased by MEG3 and was downregulated by miR-214 mimic. miRNA-214 reversed the effect of MEG3 on inhibiting cell proliferation and inducing cell apoptosis and cell cycle arrest in SUP-T1 cells. Moreover, relative expression of AIFM2 had a positive correlation with the expression of MEG3 and was negatively affected by miR-214. In vivo, MEG3 effectively suppressed tumor growth and the expression of proliferation markers Ki-67 and proliferating cell nuclear antigen (PCNA). Taken together, our research revealed that MEG3 worked as an anti-oncogene in T-LBL, and the MEG3-miR-214-AIFM2 pathway regulated the growth of T-LBL, providing potential prognosis markers as well as new potential targets for T-LBL treatment. 

Retracted: Yes

PubPeer comments:
  Figure 8. Overexpression of MEG3 inhibits tumor growth in vivo. SUP-T1 cells were transfected with LncRNA-MEG3 or MEG3 scramble and were subcutaneously injected into nude mice. (A) The representative images of T-LBL xenografts are presented . ![file] lncRNA-MEG3 row seems to be the same as in Fig 6A of [Zhang, Liang Li (2017)] . ![] That other paper purportedly used U-251 cells and had no authors in common. , 
 Fig 7. ![file] For 38 cases, the expression of miR-214 ranges from 0 to 5,and from 0 to 4.5, in the horizontal axes of A and B respectively. The expression of MEG3 ranges from 0 to 5.2, and from 0 to 4.2, in the vertical axes of A and C respectively. These graphs are plotting unrelated sets of numbers. , 
 Please be noted, the same or very similar crease of Surgical pad are showing on the following 11 chinese papers including this paper. Also, the samples on the pad are somehow shared in those papers. UCA1 Regulates the Growth and Metastasis of Pancreatic Cancer bySponging miR-135a. Oncology research (2017) . DOI: 10.3727 096504017x14888987683152. ![file] H19 promotes the migration and invasion of colon cancer by spongingmiR-138 to upregulate the expression of HMGA1. INTERNATIONAL JOURNAL OF ONCOLOGY (2017). DOI: 10.3892 ijo.2017.3941. ![file] Silencing of lncRNA CCDC26 Restrains the Growth and Migration of Glioma Cells In Vitroand In Vivo via Targeting miR-203. Oncology research (2018). DOI: 10.3727 096504017x14965095236521. ![file] Long Noncoding RNA SChLAP1 Accelerates the Proliferation and Metastasis of Prostate Cancervia Targeting miR-198 and Promoting the MAPK1 Pathway. Oncology research (2018) . DOI: 10.3727 096504017x14944585873631. ![file] HOTAIR contributes to cell proliferation and metastasis of cervical cancer via targetting MAPK1 axis. Bioscience reports (2018). DOI: 10.1042 bsr20171563. ![file] Long non-coding RNA MEG3 inhibits cell growth of gliomas by targeting miR-93 andinactivating PI3K AKT pathway. Oncology reports (2017). DOI: 10.3892 or.2017.5871. ![file] The inhibitory effect of MEG3 miR-214 AIFM2 axis on the growth of T-cell lymphoblastic lymphoma. INTERNATIONAL JOURNAL OF ONCOLOGY. DOI: 10.3892 ijo.2017.4006. ![file] Inhibition of BAMBI reduces the viability and motility of colon cancervia activating TGFu2011u03b2 Smad pathway in vitro and in vivo. ONCOLOGY LETTERS. 10.3892 ol.2017.6811. ![file] HNF1Au2011AS1 promotes growth and metastasis of esophageal squamous cellcarcinoma by sponging miRu2011214 to upregulate the expression of SOX-4. INTERNATIONAL JOURNAL OF ONCOLOGY. DOI: 10.3892 ijo.2017.4034. ![file] Astragaloside IV inhibits progression of glioma via blocking MAPK ERKsignaling pathway. Biochemical and Biophysical Research Communications (2017). DOI: 10.1016 j.bbrc.2017.07.052. ![file] Epigenetic silence of HOTAIR contributes to the metastasis of pancreaticcancer via targeting miR-138. Oncology Research (2017). DOI: 10.3727 096504017X15138544374391. ![file] Possibly the following one: Long Noncoding RNA MEG3 Inhibits Cell Proliferation and Metastasis in Chronic Myeloid Leukemia via Targeting miR-184. Oncology research (2018) . DOI: 10.3727 096504017x14980882803151 ![file] , 
 Below: Fig 3A.  Overexpression of MEG3 induces cell apoptosis and cell cycle arrest. SUP-T1 cells were transfected with lv-LncRNA-MEG3 or lv-MEG3 scramble, respectively. (A) Cell apoptosis was detected using flow cytometry. Above: Fig 2C from [Li et al (2018)] ,  HOTAIR knockdown increases apoptosis in cervical cancer cells ... (C) The cell apoptosis was analyzed by Annexin V flow cytometry. ![file] How to explain the similarity? , 
 Fig 3A again, now with colored rectangles. ![file] Scarlet is to facilitate comparison with Fig 2E from [Zhang et al (2017)] .  Flow cytometry was performed to determine the percentages of apoptosis in SW1990 and PANC-1 cells . ![file] , 
 #2 ![] But wait, it gets better! A scatterplot based on the same points is used in Fig 5E of [Li et al (2018)] , Fig 6D of [Zhang et al (2017)] , Fig 1C of [Chen et al (2019)] , Fig 3K of [Yang et al (2017)] , Fig 7A of [Fan et al (2017)] and Fig 5H of [Wang et al (2017)] . ![file] This deserves some sort of award. , 
 Retracted [22 December 2020] . ----------------------------------- Following the publication of this paper, it was drawn to the authors attention by an interested reader that a row of the tumour images featured in Fig. 8A of the above paper were strikingly similar to those featured in Fig. 6A of an article appearing in Oncology Reports that had been published by a different research group at a different institution [Zhang L, Liang X and Li Y: Long non-coding RNA MEG3 inhibits cell growth of gliomas by targeting miR-93 and inactivating PI3K AKT pathway. Oncol Rep 38: 2408-2416, 2017]. The Editor asked the authors for an explanation to account for the appearance of strikingly similar data in their paper independently, although the authors proved to be uncontactable in this regard, and did not respond to various queries. The Editor has therefore taken an executive decision to retract this paper from International Journal of Oncology without the agreement of the authors. The Editor apologizes to the readership for any inconvenience caused. ,