Research Papers:

Menin mediates Tat-induced neuronal apoptosis in brain frontal cortex of SIV-infected macaques and in Tat-treated cells

Jun Wang _, Yu Zhang, Qiping Xu, Jinhua Qiu, Honghua Zheng, Xiang Ye, Yuhua Xue, Yongmei Yin, Zhou Zhang, Ying Liu, Yanling Hao, Qiang Wei, Wei Wang, Kazuyasu Mori, Shuji Izumo, Ryuji Kubota, Yiming Shao and Hui Qin Xing

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Oncotarget. 2017; 8:18082-18094. https://doi.org/10.18632/oncotarget.14993

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Jun Wang1,*, Yu Zhang1,*, Qiping Xu1,*, Jinhua Qiu1, Honghua Zheng1, Xiang Ye1,*, Yuhua Xue2, Yongmei Yin3, Zhou Zhang4, Ying Liu4, Yanling Hao4, Qiang Wei5, Wei Wang5, Kazuyasu Mori6, Shuji Izumo7, Ryuji Kubota7, Yiming Shao4, Hui Qin Xing1

1Fujian Provincial Key Laboratory of Neurodegenerative Disease and Aging Research, Institute of Neuroscience, Department of Pathology, Basic Medicine, Medical College, Xiamen University, Xiamen, Fujian 361102, China

2School of Pharmaceutical Sciences at Xiamen University, Xiamen, Fujian 361102, China

3The Fifth People’s Hospital of Wuxi, Affiliated to Jiangnan University, Wuxi, Jiangsu 214005, China

4State Key Laboratory for Infectious Disease Prevention and Control, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, National Center for AIDS/STD Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing 102206, China

5Institute of Laboratory Animal Sciences of Chinese Academy of Medical Science, Beijing 100021, China

6AIDS Research Center, National Institute of Infectious Disease, Tokyo 862-1640, Japan

7Division of Molecular Pathology, Center for Chronic Viral Diseases, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima 890-8544, Japan

*These authors have contributed equally to this work

Correspondence to:

Hui Qin Xing, email: [email protected]

Yiming Shao, email: [email protected]

Keywords: menin, Tat, neuron, apoptosis, human immunodeficiency virus-associated neurocognitive disorder

Received: July 26, 2016    Accepted: January 03, 2017    Published: February 02, 2017


The molecular mechanisms involved in human immunodeficiency virus (HIV)-associated neurocognitive disorder (HAND) remain poorly understood. It has been recently reported that HIV-1 Tat transactivation requires menin, suggesting that menin may be involved in HAND pathogenesis. But the role of menin is not clear. Here, we found that protein level of menin was increased in simian-human immunodeficiency chimeric virus (SHIV)-SF162.P4 and simian immunodeficiency virus (SIV) sm543-3-infected rhesus macaques compared with the controls by immunohistochemistry (IHC) and western blot. Menin mainly expressed in the frontal cortex neurons of the brain, more importantly, the number of menin-staining cells was positively correlated with cleaved-caspase-3-positive cells while it was negatively correlated with a neuron-specific nuclear protein NeuN-positive cells, suggesting that expression of menin may induce neuronal apoptosis. Further studies showed that menin level was significantly increased during Tat-induced apoptosis, while downregulation of menin by pll3.7-MEN1-shRNA attenuated the Tat-induced cleavage of caspase-3 and caspase-8 in SY5Y cells and primary neuron cultures. Together, our findings reveal a pro-apoptotic role of menin in the brains of the SIV-infected macaques and the cultured neurons, indicating that targeting menin may be potential to block the HIV-1 Tat induced neuronal damage in HAND.

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