miR‐15b mediates oxaliplatin‐induced chronic neuropathic pain through BACE1 down‐regulation

Ito, Naomi; Sakai, Atsushi; Miyake, Noriko; Maruyama, Motoyo; Iwasaki, H; Miyake, Keisuke; Okada, Takashi; Sakamoto, Atsuhiro; Suzuki, Hidenori

doi:10.1111/bph.13698

Cited by 40 publications

(31 citation statements)

References 43 publications

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“…Recently, increasing studies have observed the roles of non‐coding RNAs in neuropathic pain (Ito et al, ; Su et al, ; Zhou, Xiong, Chen, Yang, & Fan, ). In our present study, we observed that XIST/miR‐544/STAT3 axis was responsible for neuropathic pain progression in CCI rats.…”

Section: Discussionmentioning

confidence: 99%

XIST/miR‐544 axis induces neuropathic pain by activating STAT3 in a rat model

Jin¹,

Du²,

Zhao³

et al. 2018

Journal Cellular Physiology

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An increasing number of studies have reported that lncRNAs are responsible for the development of neuropathic pain. In our current study, chronic constriction injury (CCI) rat models were established and we observed that lncRNA XIST was greatly increased. Knockdown of XIST can relieve pain characteristics including both mechanical and thermal hyperalgesia in CCI rats. Meanwhile, XIST down-regulation could inhibit neuro-inflammation by reducing expression of inflammatory cytokines including tumor necrosis factor (TNF)-α, IL-1β, and IL-6 and in CCI rats. By performing bioinformatics technology, miR-544 was predicted to have interactions with XIST and dual-luciferase reporter assays validated the correlation between them. A negative correlation between miR-544 and XIST was observed by carrying out XIST loss or gain of function tests. miR-544 markedly alleviated neuropathic pain development in CCI rats via targeting inflammatory cytokines, which was reversed by XIST over-expression. Moreover, STAT3 was manifested to be a target gene of miR-544 by bioinformatics predictions and it was activated in CCI rats. Over-expression of STAT3 was able to induce neuropathic pain and miR-544 inhibited this process in vivo. Furthermore, XIST increased STAT3 expression by sponging miR-544 in neuropathic pain development. To conclude, our present study indicated that XIST can contribute to neuropathic pain progression in rats through down-regulating miR-544 and up-regulating STAT3. Our results suggested that XIST/miR-544/STAT3 axis can serve as a novel therapeutic target in neuropathic pain development.

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Section: Discussionmentioning

confidence: 99%

XIST/miR‐544 axis induces neuropathic pain by activating STAT3 in a rat model

Jin¹,

Du²,

Zhao³

et al. 2018

Journal Cellular Physiology

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“…Chemotherapeutic paclitaxel produced ectopic spontaneous activity in DRG neuronal somata . This abnormal activity, which has been identified as a CIPNP contributor, may be related to the changes in the gene expression at the transcriptional and translational levels in the DRG after chemotherapy drug treatments . Understanding how chemotherapy drugs drive these changes is essential for improving patient care.…”

Section: Introductionmentioning

confidence: 99%

“…[10][11][12][13] This abnormal activity, which has been identified as a CIPNP contributor, [10][11][12][13] may be related to the changes in the gene expression at the transcriptional and translational levels in the DRG after chemotherapy drug treatments. [10][11][12][13][14][15][16][17][18][19] Understanding how chemotherapy drugs drive these changes is essential for improving patient care.…”

Section: Introductionmentioning

confidence: 99%

DNMT3a‐triggered downregulation of K_2p1.1 gene in primary sensory neurons contributes to paclitaxel‐induced neuropathic pain

Mao

et al. 2019

Intl Journal of Cancer

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Antineoplastic drugs induce dramatic transcriptional changes in dorsal root ganglion (DRG) neurons, which may contribute to chemotherapy‐induced neuropathic pain. K2p1.1 controls neuronal excitability by setting the resting membrane potential. Here, we report that systemic injection of the chemotherapy agent paclitaxel time‐dependently downregulates the expression of K 2p1.1 mRNA and its coding K2p1.1 protein in the DRG neurons. Rescuing this downregulation mitigates the development and maintenance of paclitaxel‐induced mechanical allodynia and heat hyperalgesia. Conversely, in the absence of paclitaxel administration, mimicking this downregulation decreases outward potassium current and increases excitability in the DRG neurons, leading to the enhanced responses to mechanical and heat stimuli. Mechanically, the downregulation of DRG K 2p1.1 mRNA is attributed to paclitaxel‐induced increase in DRG DNMT3a, as blocking this increase reverses the paclitaxel‐induced the decrease of DRG K2p1.1 and mimicking this increase reduces DRG K2p1.1 expression. In addition, paclitaxel injection increases the binding of DNMT3a to the K 2p1.1 gene promoter region and elevates the level of DNA methylation within this region in the DRG. These findings suggest that DNMT3a‐triggered downregulation of DRG K2p1.1 may contribute to chemotherapy‐induced neuropathic pain.

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“…6 For instance, miR-15b was reported to mediate neuropathic pain via downregulating BACE1. 7 The upregulation of miR-132-3p was correlated to chronic neuropathic pain. 8 Since miRNA has become the target of neuropathic pain therapy, it is of great value to find novel targets for neuropathic pain treatment.…”

Section: Introductionmentioning

confidence: 99%

miR‐194 relieve neuropathic pain and prevent neuroinflammation via targeting FOXA1

Zhang

Chen

Shen

et al. 2020

J of Cellular Biochemistry

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The emerging role of microRNAs (miRNAs) have been deeply explored in multiple diseases including neuropathic pain. miR-194 was widely reported to be a tumor suppressor and was related to the inflammatory response. The critical role of neuroinflammation on neuropathic pain leads to a thinking about the relationship between miR-194 and neuropathic pain. However, the function of miR-194 in neuropathic pain remains unknown. This study was aimed to explore the relationship between miR-194 and neuropathic pain progression by chronic sciatic nerve injury (CCI). miR-194 abnormally downregulated in the CCI model rat and its overexpression significantly alleviates neuroinflammation in vivo. We predict Forkhead box protein A1 (FOXA1) as a direct target of miR-194, whose restoration can markedly reverse the effects of miR-194 on neuropathic pain. Overall, our study demonstrated a novel mechanism of neuropathic pain progression that miR-194 alleviates neuropathic pain via targeting FOXA1 and preventing neuroinflammation by downregulating inflammatory cytokines containing cyclooxygenase 2, interleukin 6 (IL-6), and IL-10 in vivo, which can be reversed by the overexpression of FOXA1. , miR-194, neuroinflammation, neuropathic pain K E Y W O R D S FOXA1

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miR‐15b mediates oxaliplatin‐induced chronic neuropathic pain through BACE1 down‐regulation

Abstract: These findings suggest that miR-15b contributes to oxaliplatin-induced chronic neuropathic pain at least in part through the down-regulation of BACE1.

Cited by 40 publications

References 43 publications

XIST/miR‐544 axis induces neuropathic pain by activating STAT3 in a rat model

XIST/miR‐544 axis induces neuropathic pain by activating STAT3 in a rat model

DNMT3a‐triggered downregulation of K_2p1.1 gene in primary sensory neurons contributes to paclitaxel‐induced neuropathic pain

miR‐194 relieve neuropathic pain and prevent neuroinflammation via targeting FOXA1

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miR‐15b mediates oxaliplatin‐induced chronic neuropathic pain through BACE1 down‐regulation

Abstract: These findings suggest that miR-15b contributes to oxaliplatin-induced chronic neuropathic pain at least in part through the down-regulation of BACE1.

Cited by 40 publications

References 43 publications

XIST/miR‐544 axis induces neuropathic pain by activating STAT3 in a rat model

XIST/miR‐544 axis induces neuropathic pain by activating STAT3 in a rat model

DNMT3a‐triggered downregulation of K2p1.1 gene in primary sensory neurons contributes to paclitaxel‐induced neuropathic pain

miR‐194 relieve neuropathic pain and prevent neuroinflammation via targeting FOXA1

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DNMT3a‐triggered downregulation of K_2p1.1 gene in primary sensory neurons contributes to paclitaxel‐induced neuropathic pain