Upregulated lncRNA ADAMTS9-AS2 suppresses progression of lung cancer through inhibition of miR-223-3p and promotion of TGFBR3
Authors: Youjun Zhou
Ting Chen
Ruilian Zhao
Zuozhang Yang
Chao Liu
Quan Gong
Zhiyong Deng
Journal: IUBMB life (2018)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: TGFBR3; lncRNA ADAMTS9-AS2; lung cancer; miR-223-3p.
Affiliations: Department of Nuclear Medicine, Tumor Hospital of Yunnan Province, The Third Affiliated Hospital of Kunming Medical College, Kunming, Yunnan, People's Republic of China., Departments of Orthopaedics, Tumor Hospital of Yunnan Province, The Third Affiliated Hospital of Kunming Medical College, Kunming, Yunnan, People's Republic of China., Department of Nuclear Medicine, the Affiliated Yan'an Hospital of Kunming Medical College, Kunming, Yunnan, People's Republic of China., Department of Palliative Medicine, Tumor Hospital of Yunnan Province, The Third Affiliated Hospital of Kunming Medical College, Kunming, Yunnan, People's Republic of China., Departments of Combination of Chinese Traditional and Western Medicine, Tumor Hospital of Yunnan Province, The Third Affiliated Hospital of Kunming Medical College, Kunming, Yunnan, People's Republic of China.

Abstract:  In this study, we aimed at investigating effects of lncRNA ADAMTS9-AS2 on lung cancer progression through regulating miR-223-3p and TGFBR3 expressions. Expressions of ADAMTS9-AS2 in lung cancer tissues and cell lines were determined by reverse transcriptase polymerase chain reaction (qRT-PCR). TargetScan and miRcode were used to predict the targeting relationships, respectively. The luciferase reporter system was used to verify that the relationship among ADAMTS9-AS2, TGFBR3 and miR-223-3p. Western blot assay tested the protein level changes in TGFBR3. Cell proliferation was determined by CCK-8 assay. Cell cycle and cell apoptosis were detected by flow cytometry assay, and migration and invasion were determined by transwell assay. Tumor xenograft model was developed to study the influence of ADAMTS9-AS2 on tumor growth in vivo. qRT-PCR results demonstrated that lncADAMTS9-AS2 was lowly expressed in lung cancer tissues. High expression of ADAMTS9-AS2 in lung cancer cells significantly reduced proliferation ability and inhibited migration, as well as elevating their apoptosis rate. In vivo assay found that ADAMTS9-AS2 suppressed the lung tumor growth. Bioinformatics predicted that miR-223-3p bound directly to the ADAMTS9-AS2 and TGFBR3, which was later confirmed by luciferase reporter system. ADAMTS9-AS2 transfection increased TGFBR3 mRNA and protein expressions in lung cancer cells, but miR-223-3p transfection significantly decreased them. Besides, our results showed that miR-223-3p induced cellular apoptosis while TGFBR3 group showed the complete opposite effect. It was proved that ADAMTS9-AS2 and TGFBR3 were the direct genes of miR-223-3p. MiR-223-3p promotes proliferation, migration and invasion of lung cancer cells by targeting TGFBR3. Therefore, ADAMTS9-AS2, miR-223-3p and TGFBR3 may provide potential targets for the treatment of lung cancer patients. © 2018 IUBMB Life, 70(6):536-546, 2018. 

Retracted: No

PubPeer comments:
 The authors of this paper have very unusual sense of mathematics. For example, the operation $$S_{alpha}+S_{beta}=S_{alpha+beta}$$ cannot be bounded in a closed interval. Besides, if both $$S_{alpha}+S_{beta}=S_{alpha+beta} qquad lambda S_{alpha}=S_{lambdaalpha}$$ hold, it is not necessary to work on the set $S$. It is a common choice to work on the interval $[-t, t]$. Besides, eq.(3.1) means nothing but rescaling the interval to the unit interval $[0,1]$. The presented awkward framework is not necessary at all. ![file] ![file] , 
 Dear Rhipidura Albiventris, Thank you for your attention to our work! On the domain problem of linguistic terms, which is about another paper mentioned in the preliminary of this paper, please refer to the reply in the following links: https: pubpeer.com publications 8A4C1B92E6895CC6C534DD268C7C8F https: pubpeer.com publications B3CD7805A1D849BF3C5652817CE220 On Eq. (3.1), i agree with you that itu2019s a work to rescale the linguistic evaluation scale into the unit interval [0,1]. But, itu2019s necessary for the proposed method in this paper for the multi-granular linguistic evaluation problem, which you can refer to Example 3.3 in this paper for a more comprehensive understanding. Thatu2019s said, in the multi-granular linguistic evaluation problem discussed in this paper, there are several linguistic evaluation scales with different granularities, which are allowed to define in different intervals. Thus, for the same symbol , it maybe correspond to different linguistic terms when the related linguistic evaluation scales havenu2019t been rescaled into one interval. The calculations at this point are confusing. Eq.(3.1) is a simple but necessary way to handle this issue for the follow-up proposing method in this paper. , 
 The interested readers may refer to the following paper where a  drawback of this paper has been pointed out by the first and second authors of this paper. Yuling Zhai and Zeshui Xu. Managing individual evaluatoru2019s personalized semantic environment of linguistic term with improved vector expression in multi-granularity linguistic group decision making. Applied Soft Computing Journal 92 (2020) 106334 doi: 10.1016 j.asoc.2020.106334 See also the comment on a similar paper on https: pubpeer.com publications 07E9AD5A99031053AC0CB7D00E188F , 
 Mr. Ms. Rhipidura Albiventris, Thank you for helping to promote our papers. We have answered your questions at this link: https: pubpeer.com publications 07E9AD5A99031053AC0CB7D00E188F. In addition, research is a continuing work. I m sure every researcher understands this. Every researcher needs to first learn the previous results, discovers his own thinking, form his own thinking into new results, and then constantly improves it. This is a job that requires a lot of time and energy, as well as the abilities to continue to learn and to resist setbacks. Therefore, ethical researchers know to respect related early research results and the authors, and cite the necessary basic research references in their own papers. Even in the face of some problems of natural science, different people s ideas may not be the same, which is worth repeated consideration, right? That s why there are multiple leaders in every area at every stage of development of human society, right? For example, Riemann Integral, Riemann-Stieltjes Integral and Lebesgue Integral are treasures of Integral science, right? The Riemann Integral, rather than the Riemann-Stieltjes Integral or Lebesgue Integral, is still taught in undergraduate calculus textbooks in universities and majors all over the world. This is not only because of respect for Riemann, but also because Riemann integrals are the basis of the results of the next two integrals. It is necessary to quote and understand the previous achievements in both knowledge learning and follow-up research, isn t it? The work of G. W. F. Hegel and A. Schopenhauer are the jewels of human intelligence, aren t it? Because of this, our society has always had the opportunity to develop, right? Therefore, we respect your work, take your questions seriously, give answers one by one, and even repeat questions unrelated to your discussion and academic research. This is our respect for you and all our readers. We welcome legitimate academic discussion, but we also defend our commitment to research. ,