MicroRNA-330 Directs Downregulation of the GABA B R2 in the Pathogenesis of Pancreatic Cancer Pain
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MicroRNA-330 Directs Downregulation of the GABABR2 in the Pathogenesis of Pancreatic Cancer Pain Mei Zhu 1 & Liqin Wang 2 & Jiao Zhu 1 & Huihong Xu 1 & Kai Wei 1 & Qianbo Chen 1 & Xiaodan Wu 3 & Xuerong Miao 1 & Zhijie Lu 1 Received: 15 January 2020 / Accepted: 20 May 2020 # Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract Pancreatic cancer is one of the most aggressive and deadly malignancies with a very poor prognosis. Pancreatic cancer-induced visceral pain is very common and is generally presented among the initial symptoms in patients; such pain is strongly associated with poor quality of life, impaired functional activity, and decreased survival. However, the principal neurobiological mechanisms of pain caused by pancreatic cancer have not been fully elucidated. Accumulating studies have shown that miRNAs play a major role in chronic pain by suppressing key molecules involved in nociception. In the present study, we report that microRNA (miR)-330 is highly expressed in the spinal dorsal horn (SDH) of nude mice with pancreatic cancer pain. Mimicking pancreatic carcinoma-induced SDH miR-330 upregulation by microinjection of miR-330 mimic into the SDH significantly induced abdominal mechanical allodynia in normal nude mice. Additionally, we found that the expression of GABABR2 was significantly decreased in the SDH of nude mice with pancreatic cancer pain and was regulated directly by miR-330 both in vitro and in vivo. Furthermore, inhibition of miR-330 rescued the expression of GABABR2 and alleviated pancreatic carcinoma-induced abdominal pain hypersensitivity in nude mice with pancreatic carcinoma. These results show that miR-330 participates in the genesis of pancreatic carcinoma-induced pain hypersensitivity by inhibiting GABABR2 expression in the SDH and might be a potential therapeutic target for pancreatic cancer pain. Keywords Pancreatic cancer . Pain . miR-330 . SDH . GABABR2
Introduction Pancreatic cancer, one of the most aggressive malignant tumors, has shown an increasing prevalence, corresponding to Mei Zhu and Liqin Wang contributed equally to this work. * Xiaodan Wu [email protected] * Xuerong Miao [email protected] * Zhijie Lu [email protected] 1
Department of Anesthesiology and Intensive Care, Third Affiliated Hospital of Second Military Medical University, 225 Changhai Road, Shanghai, China
2
Department of Anesthesiology, 905th Hospital of PLAN, Shanghai, China
3
Department of Anesthesiology, Fujian Provincial Hospital, Fujian Provincial Clinical Medical College, Fujian Medical University, Fuzhou 350001, Fujian, China
the fourth most common cause of cancer death among women and the fifth most common cause among men in developed countries(Raimondi et al. 2009; Dobosz et al. 2016; Siegel et al. 2019). Pancreatic cancer-induced visceral pain, which is experienced in the upper abdomen and/or mid-back, is very common and is usually presented among the initial symptoms in patients(Foley 1988). It has been reported that 40–80% of patients suffer from pain during the p
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