Biochemical and Biophysical Research Communications
Effects of miR-150 on neuropathic pain process via targeting AKT3
Introduction
Neuropathic pain is defined as pain due to injury to somatosensory nervous system [1]. As one of the chronic pains, it is more difficult to treatment compared to other forms of pain [2]. It is a common problem in clinical practice as the prevalence in general people ranged from 6.9% to 10% [3]. It has been disturbing patients for long time and decreases their life quality. Nevertheless, the molecular mechanism of neuropathic pain progression is not satisfactory yet. New effective clinical treatment for neuropathic pain therapy is necessary to establish.
MicroRNA are small non-coding RNAs modulating gene expression through post-transcriptional control. MiRNA is found to regulating neuropathic pain in difference ways [4]. For example, MIR-96 was found to alleviate neuropathic pain through modulating voltage-gated sodium channel Nav1.3 mRNA in CCI rat model [5]. Enhanced level of miRNA-195 enhanced mechanical and cold hypersensitivity by repressing ATG14 mRNA expression [6]. MicroRNA-183 was able to restrain neuropathic pain through repressing mTOR/VEGF pathway [7]. In conclusion, miRNAs are very substantial in neuropathic pain modulating. It is of very high value to target some specific miRNAs to restrain neuropathic pain process. Therefor, miRNA can be the potential targets for neuropathic pain treatment.
AKT is a serine/threonine protein kinase. It was first identified to be a viral oncogene including 3 isoforms, AKT1, AKT2, and AKT3. Altered AKT level was associated with lots of cell physiology behaviours like apoptosis, proliferation, leading to cancer progression [8]. Besides, AKT works as a target in the downstream of phosphoinositide 3 kinase (PI3K) pathway, which is important for cell survical by regulating many cells physiology behaviours involving proliferation and angiogenesis, and can also regulate invasion of tumor [8]. AKT kinase activity in psoriasis patients is significantly higher compared to other people. High AKT expression will lead to excessive keratinocyte proliferation and dermal papillary hyperplasia (X. Y [9].
Recently, we concentrate on the effect of miR-150 in neuropathic pain process. It is reported that miR-150 was involved in various disease. MiR-150 could attenuate the progression of colorectal cancer cell EMT via inhibiting Gli1 [10]. MiR-150 also attenuate dendritic cell immune inflammatory responses through JAK1-STAT1/c-Fos signalling and keep cardiomyocytes living when treated with hypoxia [11]. Here, we supposed that miR-150 alleviated neuropathic pain via targeting AKT3.
Section snippets
Animal studies
The Sprague-Dawley rats for experiments were purchased from Shanghai Animal Laboratory Center. All of them were Adult (190–210 g) female. The rats were fed in the same condition. We isolated all of them every 5 rats to one cage. Temperature indoor was from 20 °C to 25 °C, and the humidity was maintained in 55% ± 5%. We turn on the lights at 7 o'clock in the morning and turn off at 5 o'clock in the afternoon. Food and water were sufficient. After one week, we separated all rats to different
Overexpression of miR-150 relieves neuropathic pain in vivo
For exploration of relation between miR-150 and neuropathic pain process, we overexpressed miR-150 in CCI rats by lentivirus injection. The PWT and PWL changes exhibited the restrained mechanical allodynia and thermal hyperalgesia by miR-150 (Fig. 1A,B). In blank CCI control and negative CCI control rat, two indicators including PWT and PWL were decreased compared to normal rat. When transfected with miR-150 in CCI rat, PWT and PWL would be increased but still lower than in normal rat. These
Discussion
Lately, lots of studies focused on the relationship between non-coding RNAs involving miRNA and lncRNA and neuropathic pain process because of the potentiality in diagnosis and therapy of neuropathic pain [[13], [14], [15]]. Therefor, it is of great value to study the correlation between non-coding RNAs and neuropathic pain. previously, Accumilating evidence has shown that miRNA was very critical for neuropathic pain process [16,17]; Y [18]. Before this, XIST was reported to induce neuropathic
Author contributions
Zhen Su and Wei Cai conceived the study. All authors contributed to data collection, analysis, and manuscript writing. All authors approved the final version of the manuscript.
Funding statement
Not Applicable.
Conflicts of interest
The authors declare that there is no conflict of interests.
Data availability statement
Material is available upon request.
Acknowledgment
The study was supported by department of Orthopedics and department of Anesthesiology of the Affiliated Huai'an NO.1 People's Hospital of Nanjing Medical University.
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