FOXF2 aggravates the progression of non-small cell lung cancer through targeting lncRNA H19 to downregulate PTEN
Authors: Z-J Liu
J Ding
J-W Lian
Y Fan
J-L Xu
T Hua
Journal: European review for medical and pharmacological sciences (2019)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: FOXF2; NSCLC; H19; PTEN; prognosis
Affiliations: Department of Oncology, Xi'an Chest Hospital, Xi'an, China. .

Abstract:  Objective: To illustrate the role of FOXF2 in the aggravation of the progression of non-small cell lung cancer (NSCLC) by targeting long non-coding RNA (lncRNA) H19 to down-regulate the gene of phosphate and tensin homolog deleted on chromosome ten (PTEN). Patients and methods: The relative levels of FOXF2 and H19 in NSCLC tissues and adjacent normal tissues were detected by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). The correlation between the expression levels of FOXF2 and H19 was analyzed. Kaplan-Meier curves were depicted for uncovering the prognostic value of FOXF2 in NSCLC patients. The proliferative and migratory abilities of A549 cells influenced by FOXF2 were also assessed. The interaction between FOXF2 and H19 was evaluated through chromatin immunoprecipitation (ChIP) assay and Western blot, so did the association between H19 and PTEN. Finally, rescue experiments were conducted to explore the role of FOXF2/H19/PTEN axis in regulating the viability and migration of A549 cells. Results: FOXF2 and H19 were upregulated in NSCLC and a positive correlation was observed between the two genes. High level of FOXF2 indicated a worse prognosis in NSCLC patients. The knockdown of FOXF2 attenuated the proliferative and migratory abilities of A549 cells. FOXF2 could bind to the promoter region of H19 and accelerated its transcription. Moreover, H19 could recruit EZH2 to bind to PTEN. The overexpression of H19 could reverse the regulatory effects of FOXF2 on the viability and migration of A549 cells. Conclusions: FOXF2 was upregulated in NSCLC. It accelerated the proliferative and migratory abilities of the NSCLC cells by targeting H19 to downregulate PTEN, thus aggravating the progression of NSCLC. 

Retracted: No

PubPeer comments:
 This paper is one of a set of (as of now) five papers that all share unexpected similarities. The papers are from different groups of authors at different hospitals, describing different cancer types. Yet, they share several similar features. * All five papers describe a group of 48 patients * All five papers describe the same set of GAPDH primers. One of them (the Reverse primer) does not appear to match the GAPDH mRNA sequence. * Figures 1 of all five papers show black bar graphs with error bars and a Kaplan-Meier curve with a blue and a red line * Two papers (XX Ma et al. and JL Xu et al.) share nearly identical positive correlation curves * All five papers show photos of wound healing (scratch) assays with the same background, suggesting they were all taken with the same microscope. Here is the set of papers: 1. J.-L. Xu, T. Hua, J. Ding, Y. Fan, Z.-J. Liu, J.-W. Lian - FOXF2 aggravates the progression of non-small cell lung cancer through targeting lncRNA H19 to downregulate PTEN - Eur Rev Med Pharmacol Sci 2019; 23 (24): 10796-10802 - DOI: 10.26355 eurrev_201912_19782 - Department of Oncology, Xi an Chest Hospital, Xi an, China 2. Q.-Z. Meng, C.-H. Cong, X.-J. Li, F. Zhu, X. Zhao, F.-W. Chen - METTL3 promotes the progression of nasopharyngeal carcinoma through mediating M6A modification of EZH2 - Eur Rev Med Pharmacol Sci 2020; 24 (8): 4328-4336 - DOI: 10.26355 eurrev_202004_21014 - Department of Head and Neck Surgery, Linyi Cancer Hospital, Linyi, China 3. T. Chen, J. Li, M.-H. Zhou, L.-J. Xu, T.-C. Pan - IL-6 stimulates lncRNA ZEB2-AS1 to aggravate the progression of non-small cell lung cancer through activating STAT1 - Eur Rev Med Pharmacol Sci 2020; 24 (7): 3734-3740 - DOI: 10.26355 eurrev_202004_20837 - Department of Cardiovascular Surgery, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China 4. T. Zhou, J.-J. Fang, Y.-X. Zhou, Z.-P. Li, L. Jiang, W.-W. Han, Z.-H. Zhu - Long non-coding RNA ANCR promotes progression of NSCLC by inhibiting E-Ca expression - Eur Rev Med Pharmacol Sci 2020; 24 (3): 1250-1257 - DOI: 10.26355 eurrev_202002_20178 - Department of Respiratory Medicine, Zhoushan Hospital of Zhejiang University, Zhoushan, China 5. X.-X. Ma, Z.-G. Cao, S.-L. Zhao - m6A methyltransferase METTL3 promotes the progression of prostate cancer via m6A-modified LEF1 - Eur Rev Med Pharmacol Sci 2020; 24 (7): 3565-3571 - DOI: 10.26355 eurrev_202004_20817 - Department of Urology, Nanjing First Hospital, Nanjing Medical University, Nanjing, China Here is a comparison of the Figures 1 from these papers. The very similar looking correlation curves of XX Ma et al. and JL Xu et al. have been highlighted with red boxes. ![file] Here is a comparison of the wound healing assay photos, with similar background spots highlighted in green and yellow boxes. Contrast enhanced. These appear to be irregularities in the microscope, which by itself is not a problem. But it is unexpected to see the same similarities in photos obtained across different laboratories. ![file] ![file] Could the authors please clarify how these photos look so similar? , 
 Figure 1.  The upregulation of FOXF2 in NSCLC. A, Relative level of FOXF2 in NSCLC tissues and adjacent normal tissues. B, The Kaplan-Meier curves depicted the overall survival in NSCLC patients with high level or low level of FOXF2. C, The relative level of H19 in NSCLC tissues and adjacent normal tissues. D, A positive correlation between the expressions of FOXF2 and H19 in NSCLC tissues. ![file] The median levels of FOXF2 and H19 expression in NSCLS tissues, as shown in 1A and 1C respectively, does not match the distributions shown in 1D. I am puzzled. , 
 Here is a superimposition of Figs 1D from this paper (in blue) and 1D from [Ma, Cao Zhao (2020)] (in red), to dramatise the degree of similarity. ![file] ,