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      Is Open Access

      While it is not deliberate, much of today's biomedical research contains logical and technical flaws, showing a need for corrective action

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          Abstract

          Biomedical research has advanced swiftly in recent decades, largely due to progress in biotechnology. However, this rapid spread of new, and not always-fully understood, technology has also created a lot of false or irreproducible data and artifacts, which sometimes have led to erroneous conclusions. When describing various scientific issues, scientists have developed a habit of saying “on one hand… but on the other hand…”, because discrepant data and conclusions have become omnipresent. One reason for this problematic situation is that we are not always thoughtful enough in study design, and sometimes lack enough philosophical contemplation. Another major reason is that we are too rushed in introducing new technology into our research without assimilating technical details. In this essay, we provide examples in different research realms to justify our points. To help readers test their own weaknesses, we raise questions on technical details of RNA reverse transcription, polymerase chain reactions, western blotting and immunohistochemical staining, as these methods are basic and are the base for other modern biotechnologies. Hopefully, after contemplation and reflection on these questions, readers will agree that we indeed know too little about these basic techniques, especially about the artifacts they may create, and thus many conclusions drawn from the studies using those ever-more-sophisticated techniques may be even more problematic.

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          Most cited references112

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          A coding-independent function of gene and pseudogene mRNAs regulates tumour biology

          The canonical role of messenger RNA (mRNA) is to deliver protein-coding information to sites of protein synthesis. However, given that microRNAs bind to RNAs, we hypothesized that RNAs possess a biological role in cancer cells that relies upon their ability to compete for microRNA binding and is independent of their protein-coding function. As a paradigm for the protein-coding-independent role of RNAs, we describe the functional relationship between the mRNAs produced by the PTEN tumour suppressor gene and its pseudogene (PTENP1) and the critical consequences of this interaction. We find that PTENP1 is biologically active as determined by its ability to regulate cellular levels of PTEN, and that it can exert a growth-suppressive role. We also show that PTENP1 locus is selectively lost in human cancer. We extend our analysis to other cancer-related genes that possess pseudogenes, such as oncogenic KRAS. Further, we demonstrate that the transcripts of protein coding genes such as PTEN are also biologically active. Together, these findings attribute a novel biological role to expressed pseudogenes, as they can regulate coding gene expression, and reveal a non-coding function for mRNAs.
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            Ribo-gnome: the big world of small RNAs.

            Small RNA guides--microRNAs, small interfering RNAs, and repeat-associated small interfering RNAs, 21 to 30 nucleotides in length--shape diverse cellular pathways, from chromosome architecture to stem cell maintenance. Fifteen years after the discovery of RNA silencing, we are only just beginning to understand the depth and complexity of how these RNAs regulate gene expression and to consider their role in shaping the evolutionary history of higher eukaryotes.
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              Rescuing US biomedical research from its systemic flaws.

              The long-held but erroneous assumption of never-ending rapid growth in biomedical science has created an unsustainable hypercompetitive system that is discouraging even the most outstanding prospective students from entering our profession--and making it difficult for seasoned investigators to produce their best work. This is a recipe for long-term decline, and the problems cannot be solved with simplistic approaches. Instead, it is time to confront the dangers at hand and rethink some fundamental features of the US biomedical research ecosystem.
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                Author and article information

                Journal
                Int J Med Sci
                Int J Med Sci
                ijms
                International Journal of Medical Sciences
                Ivyspring International Publisher (Sydney )
                1449-1907
                2018
                19 January 2018
                : 15
                : 4
                : 309-322
                Affiliations
                [1 ]Key Lab of Endemic and Ethnic Diseases of the Ministry of Education of China in Guizhou Medical University, Guiyang, Guizhou 550004, P. R. China
                [2 ]Molecular Biology Center, Guizhou Medical University, Guiyang, Guizhou 550004, P.R. China
                [3 ]Department of Biochemistry, China Three Gorges University, Yichang City, Hubei 443002, P.R. China
                [4 ]Hormel Institute, University of Minnesota, Austin, MN 55912, USA
                [5 ]Department of Pathology, Guizhou Medical University, Guiyang, Guizhou 550004, P.R. China
                [6 ]Clinical Research Center, Guizhou Medical University Hospital, Guiyang, Guizhou 550004, P.R. China
                [7 ]Laboratory of Cell and Molecular Biology & State Key Laboratory of Molecular Oncology, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100021, PR China
                Author notes
                ✉ Corresponding authors: Dr. Yan He, Key Lab of Endemic and Ethnic Diseases of the Ministry of Education of China in Guizhou Medical University, Guiyang, Guizhou Province 550004, P. R. China, Email: annieheyan@ 123456gmc.edu.cn ; Dr. Chengfu Yuan, Department of Biochemistry, China Three Gorges University, Yichang City, Hubei Province 443002, P.R. China, Email: yuancf46@ 123456ctgu.edu.cn ; Dr. Ningzhi Xu, Laboratory of Cell and Molecular Biology, Cancer Institute, Chinese Academy of Medical Science, Beijing 100021, China, Email: xuningzhi@ 123456cicams.ac.cn ; Dr. D. Joshua Liao, Department of Pathology, Guizhou Medical University Hospital, Guiyang, Guizhou 550004, China, Email: djliao@ 123456gmc.edu.cn

                Competing Interests: The authors have declared that no competing interest exists.

                Article
                ijmsv15p0309
                10.7150/ijms.23215
                5835702
                29511367
                06e49dc8-252f-41e9-938c-5ca592718464
                © Ivyspring International Publisher

                This is an open access article distributed under the terms of the Creative Commons Attribution (CC BY-NC) license ( https://creativecommons.org/licenses/by-nc/4.0/). See http://ivyspring.com/terms for full terms and conditions.

                History
                : 8 October 2017
                : 21 December 2017
                Categories
                Review

                Medicine
                biotechnology,reproducibility,artifacts,reverse transcription,polymerase chain reactions,microrna,sirna

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