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      Role of MiR-27a-3p in Intervertebral Disc Degeneration through Targeting RASSF5 via MST1/LATS1 and RAS/RAC1 Signaling Pathway

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      Journal of Healthcare Engineering
      Hindawi

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          Abstract

          Background

          The apoptosis of nucleus pulposus (NP) cells reduces the number of nucleus pulposus cells in intervertebral disc tissue, resulting in intervertebral disc degeneration (IDD). MicroRNAs (miRNAs) play an important regulatory role in abnormal cell proliferation and apoptosis.

          Methods

          The miR-27a-3p expressions in degenerative NP tissue and cells were measured via qPCR. The impacts of miR-27a-3p on the proliferation and apoptosis of human NP cells were evaluated by flow cytometry assays, MTT assays, and western blot analyses. In addition, target scan and luciferase reporter assay were applied to confirm that RASSF5 was directly binding to miR-27a-3p. Western blot was applied to assess the relationship between miR-27a-3p, RASSF5 and MST1/LATS1, and RAS/RAC1 signaling pathway.

          Results

          MiR-27a-3p was downregulated in degenerative NP tissues and cells by comparison with the control group. MiR-27a-3p overexpression enhanced cell proliferation and suppressed apoptosis of NP cells, while the above factors showed an opposite tendency after in the miR-27a-3p inhibitor group. The western blot experiment similarly suggested mir-27a-3p apparently downregulated apoptosis-related proteins (Bax and caspase-3) and upregulated antiapoptotic proteins (Bcl-2). In addition, RASSF5 was confirmed to be directly regulated by miR-27a-3p using the luciferase reporter assay. Overexpressed RASSF5 could reverse the effects caused by miR-27a-3p mimic. Finally, miR-27a-3p could downregulate RASSF5 and affected the MST1/LATS1 and RAS/RAC1 pathway.

          Conclusion

          MiR-27a-3p may target RASSF5 and enhance cell proliferation and imped cell apoptosis of the nucleus pulposus cells via the MST1/LATS1 and RAS/RAC1 pathway, lessening the degeneration of intervertebral discs.

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          Most cited references23

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          Low back pain: a twentieth century health care enigma.

          Despite greater knowledge, expertise, and health care resources for spinal pathologies, chronic disability resulting from nonspecific low back pain is rising exponentially in western society. Medical care certainly has not solved the everyday symptom of low back pain and even may be reinforcing and exacerbating the problem. An historic review shows that there is no change in the pathology or prevalence of low back pain: What has changed in our understanding and management. There are striking differences in health care for low back pain in the United States and the United Kingdom, although neither delivers the kind of care recommended by recent evidence-based guidelines. Medical care for low back pain in the United States is specialist-oriented, of high technology, and of high cost, but 40% of American patients seek chiropractic care for low back pain instead. National Health Service care for low back pain in the United Kingdom is underfunded, too little and too late, and 55% of British patients pay for private therapy instead. Despite the different health care systems, treatment availability, and costs, there seems to be little difference in clinical outcomes or the social impact of low back pain in the two countries. There is growing dissatisfaction with health care for low back pain on both sides of the Atlantic. Future health care for patients with nonspecific low back pain should be designed to meet their specific needs.
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            MiR-27a-3p functions as an oncogene in gastric cancer by targeting BTG2

            microRNA-27a (miR-27a) is frequently dysregulated in human carcinoma, including gastric cancer. The B-cell translocation gene 2 (BTG2) has been implicated in gastric carcinogenesis. However, till now, the link between miR-27a and BTG2 in gastric cancer has not been reported. Here, we found that two isoforms of mature miR-27a, miR-27a-5p and miR-27-3p, were both frequently overexpressed in gastric cancer tissues and cell lines, whereas the expression level of miR-27-3p in gastric cancer was significantly higher than that of miR-27a-5p. And overexpression of miR-27a-3p, but not miR-27a-5p, markedly promoted gastric cancer cell proliferation in vitro as well as tumor growth in vivo. Further experiments revealed that BTG2 was a direct and functional target of miR-27a-3p in gastric cancer and miR-27a-3p inhibition obviously up-regulated the expression of BTG2. In turn, overexpression of BTG2 triggered G1/S cell cycle arrest, induced subsequent apoptosis, and inhibited C-myc activation following Ras/MEK/ERK signaling pathway, which involved in the biological effects of miR-27a-3p/BTG2 axis on gastric carcinogenesis and cancer progression. Overall, these results suggested that the miR-27a-3p/BTG2 axis might represent a promising diagnostic biomarker for gastric cancer patients and could be a potential therapeutic target in the management of gastric cancer.
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              Integrated Genomic and Functional microRNA Analysis Identifies miR-30-5p as a Tumor Suppressor and Potential Therapeutic Nanomedicine in Head and Neck Cancer

              To identify deregulated and inhibitory microRNAs (miRNA, miR), and generate novel mimics for replacement nanomedicine for head and neck squamous cell carcinomas (HNSCC). We integrated miRNA and mRNA expression, copy number variation, and DNA methylation results from The Cancer Genome Atlas (TCGA), with a functional genome-wide screen. We reveal that the miR-30 family is commonly repressed, and all 5 members sharing these seed sequence similarly inhibit HNSCC proliferation in vitro . We uncover a previously unrecognized inverse relationship with overexpression of a network of important predicted target mRNAs deregulated in HNSCC, that includes key molecules involved in proliferation (EGFR, MET, IGF1R, IRS1, E2F7), differentiation (WNT7B, FZD2), adhesion, and invasion (ITGA6, SERPINE1). Re-expression of the most differentially repressed family member, miR-30a-5p, suppressed this mRNA program, selected signaling proteins and pathways, and inhibited cell proliferation, migration, and invasion in vitro . Further, a novel miR-30a-5p mimic formulated into a targeted nanomedicine significantly inhibited HNSCC xenograft tumor growth and target growth receptors EGFR and MET in vivo . Significantly decreased miR-30a/e family expression was related to DNA promoter hypermethylation and/or copy loss in TCGA data, and clinically with decreased disease-specific survival in a validation dataset. Strikingly, decreased miR-30e-5p distinguished oropharyngeal HNSCC with poor prognosis in TCGA (p=0.002) and validation (p=0.007) datasets, identifying a novel candidate biomarker and target for this HNSCC subset. We identify the miR-30 family as an important regulator of signal networks and tumor suppressor in a subset of HNSCC patients, that may benefit from miR replacement nanomedicine therapy.
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                Author and article information

                Contributors
                Journal
                J Healthc Eng
                J Healthc Eng
                JHE
                Journal of Healthcare Engineering
                Hindawi
                2040-2295
                2040-2309
                2022
                7 March 2022
                : 2022
                : 4457673
                Affiliations
                Department of Orthopedics, Xinqiao Hospital, Army Medical University, Chongqing 400037, China
                Author notes

                Academic Editor: Bhagyaveni M.A

                Author information
                https://orcid.org/0000-0003-3199-7045
                Article
                10.1155/2022/4457673
                8920666
                35295173
                5bdc7c5d-bd8c-466b-aae4-17233b76d773
                Copyright © 2022 Chao Yuan et al.

                This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 12 January 2022
                : 10 February 2022
                Categories
                Research Article

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