Large-scale analysis of small RNAs derived from traditional Chinese herbs in human tissues
|
摘要
Plant-derived microRNAs have recently been reported to function in human blood and tissues. Controversy was immediately raised due to possible contamination and the lack of large sample sizes. Here, we report thousands of unique small RNAs derived from traditional Chinese medicine(TCM) herbs found in human blood cells and mouse lung tissues using a large-scale analysis.We extracted small RNAs from decoctions of 10 TCM plants(Ban Zhi Lian, Chai Hu, Chuan Xin Lian, Di Ding Zi Jin, Huang Qin, Jin Yin Hua, Lian Qiao, Pu Gong Ying, Xia Ku Cao, and Yu Xing Cao) and obtained millions of RNA sequences from each herb. We also obtained RNA-Seq data from the blood cells of humans who consumed herbal decoctions and from the lung tissues of mice administered RNAs from herbal decoctions via oral gavage. We identified thousands of unique small RNA sequences in human blood cells and mouse lung tissues. Some of these identified small RNAs from Chuan Xin Lian and Hong Jing Tian could be mapped to the genomes of the herbs, confirming their TCM plant origin. Small RNAs derived from herbs regulate mammalian gene expression in a sequence-specific manner, and thus are a superior novel class of herbal drug components that hold great potential as oral gene-targeted therapeutics, highlighting the important role of herbgenomics in their development.
Plant-derived microRNAs have recently been reported to function in human blood and tissues. Controversy was immediately raised due to possible contamination and the lack of large sample sizes. Here, we report thousands of unique small RNAs derived from traditional Chinese medicine(TCM) herbs found in human blood cells and mouse lung tissues using a large-scale analysis.We extracted small RNAs from decoctions of 10 TCM plants(Ban Zhi Lian, Chai Hu, Chuan Xin Lian, Di Ding Zi Jin, Huang Qin, Jin Yin Hua, Lian Qiao, Pu Gong Ying, Xia Ku Cao, and Yu Xing Cao) and obtained millions of RNA sequences from each herb. We also obtained RNA-Seq data from the blood cells of humans who consumed herbal decoctions and from the lung tissues of mice administered RNAs from herbal decoctions via oral gavage. We identified thousands of unique small RNA sequences in human blood cells and mouse lung tissues. Some of these identified small RNAs from Chuan Xin Lian and Hong Jing Tian could be mapped to the genomes of the herbs, confirming their TCM plant origin. Small RNAs derived from herbs regulate mammalian gene expression in a sequence-specific manner, and thus are a superior novel class of herbal drug components that hold great potential as oral gene-targeted therapeutics, highlighting the important role of herbgenomics in their development.
Plant-derived microRNAs have recently been reported to function in human blood and tissues. Controversy was immediately raised due to possible contamination and the lack of large sample sizes. Here, we report thousands of unique small RNAs derived from traditional Chinese medicine(TCM) herbs found in human blood cells and mouse lung tissues using a large-scale analysis.We extracted small RNAs from decoctions of 10 TCM plants(Ban Zhi Lian, Chai Hu, Chuan Xin Lian, Di Ding Zi Jin, Huang Qin, Jin Yin Hua, Lian Qiao, Pu Gong Ying, Xia Ku Cao, and Yu Xing Cao) and obtained millions of RNA sequences from each herb. We also obtained RNA-Seq data from the blood cells of humans who consumed herbal decoctions and from the lung tissues of mice administered RNAs from herbal decoctions via oral gavage. We identified thousands of unique small RNA sequences in human blood cells and mouse lung tissues. Some of these identified small RNAs from Chuan Xin Lian and Hong Jing Tian could be mapped to the genomes of the herbs, confirming their TCM plant origin. Small RNAs derived from herbs regulate mammalian gene expression in a sequence-specific manner, and thus are a superior novel class of herbal drug components that hold great potential as oral gene-targeted therapeutics, highlighting the important role of herbgenomics in their development.
引文
Ambros,V.(2004).The functions of animal microRNAs.Nature 431,350-355.
Bartel,D.P.(2004).microRNAs.Cell 116,281-297.
Bartel,D.P.(2009).microRNAs:target recognition and regulatory functions.Cell 136,215-233.
Beatty,M.,Guduric-Fuchs,J.,Brown,E.,Bridgett,S.,Chakravarthy,U.,Hogg,R.E.,and Simpson,D.A.(2014).Small RNAs from plants,bacteria and fungi within the order Hypocreales are ubiquitous in human plasma.BMC Genomics 15,933.
Bennett,C.F.,and Swayze,E.E.(2010).RNA targeting therapeutics:molecular mechanisms of antisense oligonucleotides as a therapeutic platform.Annu Rev Pharmacol Toxicol 50,259-293.
Chen,S.L.,and Song,J.Y.(2016).Herbgenomics(in Chinese).Zhongguo Zhong Yao Za Zhi 41,3881-3889.
Crooke,S.T.(2017).Molecular mechanisms of antisense oligonucleotides.Nucleic Acid Therapeut 27,70-77.
Dickinson,B.,Zhang,Y.,Petrick,J.S.,Heck,G.,Ivashuta,S.,and Marshall,W.S.(2013).Lack of detectable oral bioavailability of plant microRNAs after feeding in mice.Nat Biotechnol 31,965-967.
Du,J.,Liang,Z.,Xu,J.,Zhao,Y.,Li,X.,Zhang,Y.,Zhao,D.,Chen,R.,Liu,Y.,Joshi,T.,et al.(2017).Plant-derived phosphocholine facilitates cellular uptake of anti-pulmonary fibrotic HJT-sRNA-m7.Sci China Life Sci doi:10.1007/s11427-017-9026-7.
Fabris,L.,and Calin,G.A.(2016).Circulating free xeno-microRNAs-The new kids on the block.Mol Oncol 10,503-508.
Fu,Y.,Li,L.,Hao,S.,Guan,R.,Fan,G.,Shi,C.,Wan,H.,Chen,W.,Zhang,H.,Liu,G.,et al.(2017).Draft genome sequence of the Tibetan medicinal herb Rhodiola crenulata.GigaScience 6,1-5.
Gunawardane,L.S.,Saito,K.,Nishida,K.M.,Miyoshi,K.,Kawamura,Y.,Nagami,T.,Siomi,H.,and Siomi,M.C.(2007).A slicer-mediated mechanism for repeat-associated siRNA 5′end formation in Drosophila.Science 315,1587-1590.
Inner Canon of Huangdi.ISBN9787514902181.
Jin,R.,Zhang,B.,Xue,C.M.,Liu,S.M.,Zhao,Q.,and Li,K.(2011).Classification of 365 Chinese medicines in Shennong’s Materia Medica Classic based on a semi-supervised incremental clustering method.JChin Integr Med 9,665-674.
Juliano,R.L.(2016).The delivery of therapeutic oligonucleotides.Nucleic Acids Res 44,6518-6548.
Kole,R.,Krainer,A.R.,and Altman,S.(2012).RNA therapeutics:beyond RNA interference and antisense oligonucleotides.Nat Rev Drug Discov11,125-140.
Lei,L.,Steffen,J.G.,Osborne,E.J.,and Toomajian,C.(2017).Plant organ evolution revealed by phylotranscriptomics in Arabidopsis thaliana.Sci Rep 7,7567.
Lin,Y.K.,Chang,Y.C.,Hui,R.C.Y.,See,L.C.,Chang,C.J.,Yang,C.H.,and Huang,Y.H.(2015).A Chinese herb,indigo naturalis,extracted in oil(Lindioil)used topically to treat psoriatic nails.JAMA Dermatol151,672-674.
Razavi,B.M.,and Hosseinzadeh,H.(2017).Saffron:a promising natural medicine in the treatment of metabolic syndrome.J Sci Food Agric 97,1679-1685.
Sano,N.,Kim,J.S.,Onda,Y.,Nomura,T.,Mochida,K.,Okamoto,M.,Seo,M.(2017).RNA-Seq using bulked recombinant inbred line populations uncovers the importance of brassinosteroid for seed longevity after priming treatments.Sci Rep 7,8095.
Shennong’s material medica classic.ISBN:9787530469033.
Shu,J.,Chiang,K.,Zempleni,J.,and Cui,J.(2015).Computational characterization of exogenous microRNAs that can be transferred into human circulation.PLoS ONE 10,e0140587.
Stein,C.A.,and Castanotto,D.(2017).FDA-approved oligonucleotide therapies in 2017.Mol Ther 25,1069-1075.
Storz,G.(2002).An expanding universe of noncoding RNAs.Science 296,1260-1263.
The Chinese Pharmacopeia.(2015).ISBN:9787506773379.
Unschuld,P.U.(1986).Medicine in China:A history of Pharmaceutics(Berkeley:University of California).
Vuppalanchi,R.,Liang,T.,Goswami,C.P.,Nalamasu,R.,Li,L.,Jones,D.,Wei,R.,Liu,W.,Sarasani,V.,Janga,S.C.,et al.(2013).Relationship between differential hepatic microRNA expression and decreased hepatic cytochrome P450 3A activity in cirrhosis.PLoS ONE 8,e74471.
Wang,M.,Dong,Q.,Wang,H.,He,Y.,Chen,Y.,Zhang,H.,Wu,R.,Chen,X.,Zhou,B.,He,J.,et al.(2016).Oblongifolin M,an active compound isolated from a Chinese medical herb Garcinia oblongifolia,potently inhibits enterovirus 71 reproduction through downregulation of ERp57.Oncotarget 7,8797-8808.
Witwer,K.W.,McAlexander,M.A.,Queen,S.E.,and Adams,R.J.(2013).Real-time quantitative PCR and droplet digital PCR for plant miRNAs in mammalian blood provide little evidence for general uptake of dietary miRNAs.RNA Biol 10,1080-1086.
Yang,H.,Li,W.,Wang,L.,Li,W.,Sun,H.,He,X.,and Zhang,J.(2017).The protective effects of sika deer antler protein on cisplatin-induced nephrotoxicity.Cell Physiol Biochem 43,395-404.
Zamecnik,P.C.,and Stephenson,M.L.(1978).Inhibition of Rous sarcoma virus replication and cell transformation by a specific oligodeoxynucleotide.Proc Natl Acad Sci USA 75,280-284.
Zhang,L.,Hou,D.,Chen,X.,Li,D.,Zhu,L.,Zhang,Y.,Li,J.,Bian,Z.,Liang,X.,Cai,X.,et al.(2012).Exogenous plant MIR168a specifically targets mammalian LDLRAP1:evidence of cross-kingdom regulation by microRNA.Cell Res 22,107-126.
Zhao,Q.,Liu,Y.,Zhang,N.,Hu,M.,Zhang,H.,Joshi,T.,and Xu,D.(2018).Evidence for plant-derived xenomiRs based on a large-scale analysis of public small RNA sequencing data from human samples.PLoS ONE 13,e0187519.
Zhou,H.,Luo,D.,GholamHosseini,H.,Li,Z.,and He,J.(2017).Identification of Chinese herbal medicines with electronic nose technology:applications and challenges.Sensors 17,1073.
Zhu,C.,Li,X.,Zhang,B.,and Lin,Z.(2017).Quantitative analysis of multi-components by single marker-a rational method for the internal quality of Chinese herbal medicine.Integr Med Res 6,1-11.
Bartel,D.P.(2004).microRNAs.Cell 116,281-297.
Bartel,D.P.(2009).microRNAs:target recognition and regulatory functions.Cell 136,215-233.
Beatty,M.,Guduric-Fuchs,J.,Brown,E.,Bridgett,S.,Chakravarthy,U.,Hogg,R.E.,and Simpson,D.A.(2014).Small RNAs from plants,bacteria and fungi within the order Hypocreales are ubiquitous in human plasma.BMC Genomics 15,933.
Bennett,C.F.,and Swayze,E.E.(2010).RNA targeting therapeutics:molecular mechanisms of antisense oligonucleotides as a therapeutic platform.Annu Rev Pharmacol Toxicol 50,259-293.
Chen,S.L.,and Song,J.Y.(2016).Herbgenomics(in Chinese).Zhongguo Zhong Yao Za Zhi 41,3881-3889.
Crooke,S.T.(2017).Molecular mechanisms of antisense oligonucleotides.Nucleic Acid Therapeut 27,70-77.
Dickinson,B.,Zhang,Y.,Petrick,J.S.,Heck,G.,Ivashuta,S.,and Marshall,W.S.(2013).Lack of detectable oral bioavailability of plant microRNAs after feeding in mice.Nat Biotechnol 31,965-967.
Du,J.,Liang,Z.,Xu,J.,Zhao,Y.,Li,X.,Zhang,Y.,Zhao,D.,Chen,R.,Liu,Y.,Joshi,T.,et al.(2017).Plant-derived phosphocholine facilitates cellular uptake of anti-pulmonary fibrotic HJT-sRNA-m7.Sci China Life Sci doi:10.1007/s11427-017-9026-7.
Fabris,L.,and Calin,G.A.(2016).Circulating free xeno-microRNAs-The new kids on the block.Mol Oncol 10,503-508.
Fu,Y.,Li,L.,Hao,S.,Guan,R.,Fan,G.,Shi,C.,Wan,H.,Chen,W.,Zhang,H.,Liu,G.,et al.(2017).Draft genome sequence of the Tibetan medicinal herb Rhodiola crenulata.GigaScience 6,1-5.
Gunawardane,L.S.,Saito,K.,Nishida,K.M.,Miyoshi,K.,Kawamura,Y.,Nagami,T.,Siomi,H.,and Siomi,M.C.(2007).A slicer-mediated mechanism for repeat-associated siRNA 5′end formation in Drosophila.Science 315,1587-1590.
Inner Canon of Huangdi.ISBN9787514902181.
Jin,R.,Zhang,B.,Xue,C.M.,Liu,S.M.,Zhao,Q.,and Li,K.(2011).Classification of 365 Chinese medicines in Shennong’s Materia Medica Classic based on a semi-supervised incremental clustering method.JChin Integr Med 9,665-674.
Juliano,R.L.(2016).The delivery of therapeutic oligonucleotides.Nucleic Acids Res 44,6518-6548.
Kole,R.,Krainer,A.R.,and Altman,S.(2012).RNA therapeutics:beyond RNA interference and antisense oligonucleotides.Nat Rev Drug Discov11,125-140.
Lei,L.,Steffen,J.G.,Osborne,E.J.,and Toomajian,C.(2017).Plant organ evolution revealed by phylotranscriptomics in Arabidopsis thaliana.Sci Rep 7,7567.
Lin,Y.K.,Chang,Y.C.,Hui,R.C.Y.,See,L.C.,Chang,C.J.,Yang,C.H.,and Huang,Y.H.(2015).A Chinese herb,indigo naturalis,extracted in oil(Lindioil)used topically to treat psoriatic nails.JAMA Dermatol151,672-674.
Razavi,B.M.,and Hosseinzadeh,H.(2017).Saffron:a promising natural medicine in the treatment of metabolic syndrome.J Sci Food Agric 97,1679-1685.
Sano,N.,Kim,J.S.,Onda,Y.,Nomura,T.,Mochida,K.,Okamoto,M.,Seo,M.(2017).RNA-Seq using bulked recombinant inbred line populations uncovers the importance of brassinosteroid for seed longevity after priming treatments.Sci Rep 7,8095.
Shennong’s material medica classic.ISBN:9787530469033.
Shu,J.,Chiang,K.,Zempleni,J.,and Cui,J.(2015).Computational characterization of exogenous microRNAs that can be transferred into human circulation.PLoS ONE 10,e0140587.
Stein,C.A.,and Castanotto,D.(2017).FDA-approved oligonucleotide therapies in 2017.Mol Ther 25,1069-1075.
Storz,G.(2002).An expanding universe of noncoding RNAs.Science 296,1260-1263.
The Chinese Pharmacopeia.(2015).ISBN:9787506773379.
Unschuld,P.U.(1986).Medicine in China:A history of Pharmaceutics(Berkeley:University of California).
Vuppalanchi,R.,Liang,T.,Goswami,C.P.,Nalamasu,R.,Li,L.,Jones,D.,Wei,R.,Liu,W.,Sarasani,V.,Janga,S.C.,et al.(2013).Relationship between differential hepatic microRNA expression and decreased hepatic cytochrome P450 3A activity in cirrhosis.PLoS ONE 8,e74471.
Wang,M.,Dong,Q.,Wang,H.,He,Y.,Chen,Y.,Zhang,H.,Wu,R.,Chen,X.,Zhou,B.,He,J.,et al.(2016).Oblongifolin M,an active compound isolated from a Chinese medical herb Garcinia oblongifolia,potently inhibits enterovirus 71 reproduction through downregulation of ERp57.Oncotarget 7,8797-8808.
Witwer,K.W.,McAlexander,M.A.,Queen,S.E.,and Adams,R.J.(2013).Real-time quantitative PCR and droplet digital PCR for plant miRNAs in mammalian blood provide little evidence for general uptake of dietary miRNAs.RNA Biol 10,1080-1086.
Yang,H.,Li,W.,Wang,L.,Li,W.,Sun,H.,He,X.,and Zhang,J.(2017).The protective effects of sika deer antler protein on cisplatin-induced nephrotoxicity.Cell Physiol Biochem 43,395-404.
Zamecnik,P.C.,and Stephenson,M.L.(1978).Inhibition of Rous sarcoma virus replication and cell transformation by a specific oligodeoxynucleotide.Proc Natl Acad Sci USA 75,280-284.
Zhang,L.,Hou,D.,Chen,X.,Li,D.,Zhu,L.,Zhang,Y.,Li,J.,Bian,Z.,Liang,X.,Cai,X.,et al.(2012).Exogenous plant MIR168a specifically targets mammalian LDLRAP1:evidence of cross-kingdom regulation by microRNA.Cell Res 22,107-126.
Zhao,Q.,Liu,Y.,Zhang,N.,Hu,M.,Zhang,H.,Joshi,T.,and Xu,D.(2018).Evidence for plant-derived xenomiRs based on a large-scale analysis of public small RNA sequencing data from human samples.PLoS ONE 13,e0187519.
Zhou,H.,Luo,D.,GholamHosseini,H.,Li,Z.,and He,J.(2017).Identification of Chinese herbal medicines with electronic nose technology:applications and challenges.Sensors 17,1073.
Zhu,C.,Li,X.,Zhang,B.,and Lin,Z.(2017).Quantitative analysis of multi-components by single marker-a rational method for the internal quality of Chinese herbal medicine.Integr Med Res 6,1-11.