microRNA-329 reduces bone cancer pain through the LPAR1-dependent LPAR1/ERK signal transduction pathway in mice
XP Wu, YP Yang, RX She, ZM Xing… - … in medical oncology, 2019 - journals.sagepub.com
XP Wu, YP Yang, RX She, ZM Xing, HW Chen, YW Zhang
Therapeutic advances in medical oncology, 2019•journals.sagepub.comBackground: Bone cancer pain (BCP) is a common symptom occurring among patients with
cancer and has a detrimental effect on their quality of life. Growing evidence has implicated
microRNA-329 (miR-329) in the progression of bone diseases. In the present study, we
aimed to elucidate the potential effects of miR-329 on BCP in a BCP mouse model via
binding to lysophosphatidic acid receptor 1 (LPAR1) through the LPAR1/extracellular signal-
regulated kinase (ERK) signaling pathway. Methods: Initially, a BCP mouse model was …
cancer and has a detrimental effect on their quality of life. Growing evidence has implicated
microRNA-329 (miR-329) in the progression of bone diseases. In the present study, we
aimed to elucidate the potential effects of miR-329 on BCP in a BCP mouse model via
binding to lysophosphatidic acid receptor 1 (LPAR1) through the LPAR1/extracellular signal-
regulated kinase (ERK) signaling pathway. Methods: Initially, a BCP mouse model was …
Background
Bone cancer pain (BCP) is a common symptom occurring among patients with cancer and has a detrimental effect on their quality of life. Growing evidence has implicated microRNA-329 (miR-329) in the progression of bone diseases. In the present study, we aimed to elucidate the potential effects of miR-329 on BCP in a BCP mouse model via binding to lysophosphatidic acid receptor 1 (LPAR1) through the LPAR1/extracellular signal-regulated kinase (ERK) signaling pathway.
Methods
Initially, a BCP mouse model was established via injection of 4 × 104 murine breast tumor (4T1 cell) cells (4 μl). The interaction between miR-329 and LPAR1 was identified using a bioinformatics website and dual luciferase reporter gene assay. The modeled mice were subsequently treated with miR-329 mimic, LPAR1 shRNA, or both, in order to examine the effect of miR-329 on the paw withdrawal threshold (PWT) and paw withdrawal latency (PWL) of mice, the expression of LPAR1/ERK signaling pathway-related genes.
Results
The positive expression rate of LPAR1 protein and extent of ERK1/2 phosphorylation were increased in BCP mouse models. LPAR1 is a target gene of miR-329, which can inhibit the expression of LPAR1. In response to miR-329 overexpression and LPAR1 silencing, BCP mice showed increased PWT and PWL, along with decreased LPAR1 expression and ratio of p-ERK/ERK.
Conclusions
Altogether, the results obtained indicated that miR-329 can potentially alleviate BCP in mice via the inhibition of LPAR1 and blockade of the LPAR1/ERK signaling pathway, highlighting that upregulation of miR-329 could serve as a therapeutic target for BCP treatment.
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