Pharmaco-resistance is a challenging problem for treatment of status epilepticus (SE) in the clinic. P-glycoprotein (P-gp) is one of the most important multi-drug transporters that contribute to drug resistance of SE. Long noncoding RNAs (lncRNAs) have been increasingly recognized as versatile regulators of P-gp in tumors and epilepsy. However, the function of lncRNAs in drug resistance of SE remains largely unknown. In the present study, pilocarpine-induced rat model is used to explore the expression profiles of lncRNAs in the hippocampus of SE using RNA sequencing. Our results implied that the level of lncRNA H19 was significantly increased in the hippocampus of SE rats, which was positively correlated with the level of P-gp. While downregulation of H19 could inhibit the expression of P-gp and alleviate neural damage in the hippocampus of SE rats. Furthermore, it was revealed that H19 regulates P-gp expression through the nuclear factor-kappaB (NF-κB) signaling pathway by functioning as a competing endogenous RNA against microRNA-29a-3p. Overall, our study indicated that H19 regulates P-gp expression and neural damage induced by SE through the NF-κB signaling pathway, which provides a promising target to overcome drug resistance and alleviate brain damage for SE.
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http://dx.doi.org/10.1007/s11064-022-03803-w | DOI Listing |
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Key Laboratory of Multi-Cell Systems, Shanghai Key Laboratory of Molecular Andrology, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China.
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Institute of Global Health and Human Ecology (IGHHE), School of Sciences and Engineering, The American University in Cairo, New Cairo 11835, Egypt. Electronic address:
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Department of Biostatistics, School of Public Health, Harbin Medical University, Harbin 150081, China.
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