The answer to the question Why have microRNA biomarkers not been translated from bench to clinic? appears in SETD3 is regulated by a couple of microRNAs and plays opposing roles in proliferation and metastasis of hepatocellular carcinoma 10/22/19
These findings were in line with the study conducted by Cheng et al. , who reported that SETD3 could be phosphorylated by the kinase glycogen synthase kinase 3 (GSK3b), which induced the FBXW7-mediated ubiquitination and degradation for SETD3. As an established post-transcriptional regulator, miRNA played important roles in facilitating degradation or blocking translation for many histone methyltransferases. In HCC, underexpression of miR-29a contribute to the up-regulation of SETDB1 . Underexpression of miR-125b also facilitates SUV39H1 overexpression . In this study, we identified that SETD3 could be regulated by a couple of miRNAs (miR-16, miR-195 and miR-497) at the post-transcriptional step, while the mRNA level of SETD3 was not significantly altered by these miRNAs. These results provided a new avenue to explain the inconsistence of SETD3 between mRNA and protein levels.
The ‘inconsistence’ arises in the context of the energy-dependent light-activated assembly of the microRNA-RNA-peptide nanocomplex, which links the Creation of oxygen from the Creation of sunlight and water to oxidative phosphorylation, which biophysically constrains viral latency in all cell types of all individuals in all species that develop tissue-specific cancers.
Conflicts of interests among those who do not want to cure cancer ensure that drug developers outside Iran and China “follow the money,” not the scientific truth about oxidative phophorylation and biophysically constrained viral latency. The scientific truth can be viewed in the context of specialization by the drug developers who ignore it.
For comparison, see: Range: Why Generalists Triumph in a Specialized World 5/28/19
My summary: When he learned what was known about geology, Darwin went wrong. He turned to the ‘left.’ His “Conditions of life” (aka sunlight, water + oxygen-dependent ecological adaptations) across 5-10,000 years, changed to speculation about conditions of death.
Others turned to the ‘left’ when they linked theories about millions of years of evolution to drug development.
Nothing was known to Darwin about the biophysically constrained energy-dependent functional structure of supercoiled DNA. Still, he repeatedly asserted the fact that “conditions of life” must come before natural selection. His “conditions of life” are still missing from the leftist perspectives of biologically uninformed science idiots. For example, most Democrats and other libtards seem to think that We are all mutants 3/16/14.
But see this advertisement: Amino acid analyzers help the search for new biotherapeutics
The use of high-throughput peptide screening technology can overcome challenges in novel drug discovery from natural sources.
Natural sources, such as food energy, biophysically constrain viral latency via the pheromone-controlled physiology of reproduction.
…miRNAs can regulate cell autophagy by modulating targetting gene expression. In this review, we will provide an overview of lncRNAs and miRNAs in autophagy modulation and new insights into the underlying mechanisms, as well as their potential utilization in disease diagnosis, prognosis, and therapy.
…the proposed mechanism of food perception will stimulate further research on neuroendocrine brain-to-gut communication and may open the possibility for therapeutic interventions to improve proteostasis and organismal health via the sense of smell…
Here is the recently clarified link from the nutrient-dependent pheromone-controlled physiology of reproduction in nematodes to healthy human longevity via the sense of smell.
1) Phosphoinositide 3-kinases (PI3Ks) are divided into three isoforms (class I, class II, and class III). The class I PI3K triggers mTOR signaling pathway and inhibits autophagy, while the class III isoform activates the autophagy by corresponding to Vps34.
2) Autophagy has been reported to either inhibit or promote cancer cell proliferation or tumorigenesis in model systems, suggesting that the role of autophagy in cancer is context dependent [6,7]. Moderate and effective autophagy can remove tumor cells and maintain homeostasis. However, impaired autophagy may reduce cell viability, and delayed elimination of apoptotic cells from the body may induce the development of cancer .
This citation obfuscates cause and effect via use of the term isoform-specific signalling.
5. Vanhaesebroeck B., et al. (2010) The emerging mechanisms of isoform-specific PI3K signalling. Nat. Rev. Mol. Cell Biol. 11, 329–341 10.1038/nrm2882
The light-activated assembly of the microRNA-RNA-peptide nanocomplex is required for all energy-dependent isoform-specific signalling. That fact is buried in the extant literature via use of terms like these:
These isoforms do not automagically create themselves.
Medical Definition of isoform. : any of two or more functionally similar proteins that have a similar but not identical amino acid sequence and are either encoded by different genes or by RNA transcripts from the same gene which have had different exons removed.
See for comparison: Gene isoform
Gene isoforms are mRNAs that are produced from the same locus but are different in their transcription start sites (TSSs), protein coding DNA sequences (CDSs) and/or untranslated regions (UTRs), potentially altering gene function.
Look at the definitions of all the highlighted/underlined terms, and you may be able to link food energy-dependent pheromone-controlled authphagy to the prevention of all virus-driven diseases because “The synthesis of RNA in isolated thymus nuclei is ATP dependent.” (1964)
If mutations led to the synthesis of RNA, there would be no need for autophagy.
Autophagy is the body’s way of cleaning out damaged cells, in order to regenerate newer, healthier cells…
Autophagy links the energy-dependent Creation of endogenous substrates to ecological adaptations, or from the virus-driven degradation of messenger RNA to mutations and all pathology. That fact does not exemplify any degree of so called evolutionary conservation. It exemplifies that fact that energy-dependent endogenous substrates, aka microRNAs, do not Create themselves.
The conflict between claims made by neo-Darwinian theorists and serious scientists has been placed into the context of The conflict between adaptation and dispersal for maintaining biodiversity in changing environments 9/30/19
These findings highlight the need to consider ecological and evolutionary processes together, or we risk underestimating how global change will impact biodiversity.
That fact presciently led to the teaching of evolution in Israeli middle schools.
…learning about evolution is not the primary function of the decision, but rather to use it as a building block for students to learn more about their ecology.
The ecologically relevant patented cure for all virus-driven cancer was issued to researchers from Israel on 12/25/18.
See also: Pathogenic role of exosomes and microRNAs in HPV-mediated inflammation and cervical cancer: A review (from researchers in Iran).
Exosomes have recently been recognized to be involved in inflammatory processes and can also affect the immune response. In this review, we discuss the role of HPV proteins, miRNAs and exosomes in the inflammation associated with CC.
“…our findings revealed a novel miR-133a-3p/MAML1/DNMT3A positive feedback loop in breast cancer cells, which may become a potential therapeutic target for breast cancer.”
Food energy-dependent microRNA-mediated autophagy is the cure for breast cancer and all other cancers. The metabolism of food to pheromones links negative feedback loops to the prevention of all pathology via microRNA-mediated RNA interference.
…the fate of hAFSCs after treatment may depend upon the interplay between the miRNAs.”
Who didn’t already know that?