[KSCI] Korea Science Citation Index Service

http://dx.doi.org/10.14348/molcells.2016.0013

MicroRNA Target Recognition: Insights from Transcriptome-Wide Non-Canonical Interactions

Seok, Heeyoung (Division of Life Sciences, College of Life Sciences and Biotechnology, Korea University)
Ham, Juyoung (Department of Health Sciences and Technology, Samsung Advanced Institute for Health Sciences and Technology, Sungkyunkwan University)
Jang, Eun-Sook (EncodeGEN Co. Ltd.)
Chi, Sung Wook (Division of Life Sciences, College of Life Sciences and Biotechnology, Korea University)

Abstract

MicroRNAs (miRNAs) are small non-coding RNAs (~22 nucleotides) regulating gene expression at the post-transcriptional level. By directing the RNA-induced silencing complex (RISC) to bind specific target mRNAs, miRNA can repress target genes and affect various biological phenotypes. Functional miRNA target recognition is known to majorly attribute specificity to consecutive pairing with seed region (position 2-8) of miRNA. Recent advances in a transcriptome-wide method of mapping miRNA binding sites (Ago HITS-CLIP) elucidated that a large portion of miRNA-target interactions in vivo are mediated not only through the canonical "seed sites" but also via non-canonical sites (~15-80%), setting the stage to expand and determine their properties. Here we focus on recent findings from transcriptome-wide non-canonical miRNA-target interactions, specifically regarding "nucleation bulges" and "seed-like motifs". We also discuss insights from Ago HITS-CLIP data alongside structural and biochemical studies, which highlight putative mechanisms of miRNA target recognition, and the biological significance of these non-canonical sites mediating marginal repression.

Keywords

argonaute; CLIP; microRNA; non-canonical targets;

Citations & Related Records

Times Cited By KSCI : 3 (Citation Analysis)

Reference
Cited By KSCI

1	Schirle, N.T., and MacRae, I.J. (2012). The crystal structure of human Argonaute2. Science 336, 1037-1040. DOI
2	Schirle, N.T., Sheu-Gruttadauria, J., and MacRae, I.J. (2014). Structural basis for microRNA targeting. Science 346, 608-613. DOI
3	Selbach, M., Schwanhausser, B., Thierfelder, N., Fang, Z., Khanin, R., and Rajewsky, N. (2008). Widespread changes in protein synthesis induced by microRNAs. Nature 455, 58-63. DOI
4	Seok, H., Jang, E.S., and Chi, S.W. (2016). Rationally designed siRNAs without miRNA-like off-target repression. BMB Rep. 49, 135-136. DOI
5	Shin, C., Nam, J.W., Farh, K.K., Chiang, H.R., Shkumatava, A., and Bartel, D.P. (2010). Expanding the microRNA targeting code: functional sites with centered pairing. Mol. Cell 38, 789-802. DOI
6	Sim, S.E., Bakes, J., and Kaang, B.K. (2014). Neuronal activitydependent regulation of microRNAs. Mol. Cells 37, 511-517. DOI
7	Stark, A., Brennecke, J., Russell, R.B., and Cohen, S.M. (2003). Identification of Drosophila microRNA targets. PLoS Biol. 1, E60. DOI
8	Stefani, G., and Slack, F.J. (2012). A 'pivotal' new rule for microRNA-mRNA interactions. Nat. Struct Mol. Biol. 19, 265-266. DOI
9	Tay, Y., Zhang, J., Thomson, A.M., Lim, B., and Rigoutsos, I. (2008). MicroRNAs to Nanog, Oct4 and Sox2 coding regions modulate embryonic stem cell differentiation. Nature 455, 1124-1128. DOI
10	Tomari, Y., and Zamore, P.D. (2005). Perspective: machines for RNAi. Genes Dev. 19, 517-529. DOI
11	Ule, J. (2003). CLIP identifies Nova-regulated RNA networks in the brain. Science 302, 1212-1215. DOI
12	Vella, M.C., Choi, E.Y., Lin, S.Y., Reinert, K., and Slack, F.J. (2004). The C. elegans microRNA let-7 binds to imperfect let-7 complementary sites from the lin-41 3[prime]UTR. Genes Dev. 18, 132-137. DOI
13	Wang, Y., Juranek, S., Li, H., Sheng, G., Wardle, G.S., Tuschl, T., and Patel, D.J. (2009). Nucleation, propagation and cleavage of target RNAs in Ago silencing complexes. Nature 461, 754-761. DOI
14	Wee, L.M., Flores-Jasso, C.F., Salomon, W.E., and Zamore, P.D. (2012). Argonaute divides its RNA guide into domains with distinct functions and RNA-binding properties. Cell 151, 1055-1067. DOI
15	Wightman, B., Ha, I., and Ruvkun, G. (1993). Posttranscriptional regulation of the heterochronic gene lin-14 by lin-4 mediates temporal pattern formation in C. elegans. Cell 75, 855-862. DOI
16	Xie, X., Lu, J., Kulbokas, E.J., Golub, T.R., Mootha, V., Lindblad-Toh, K., Lander, E.S., and Kellis, M. (2005). Systematic discovery of regulatory motifs in human promoters and 3' UTRs by comparison of several mammals. Nature 434, 338-345. DOI
17	Xue, Y., Ouyang, K., Huang, J., Zhou, Y., Ouyang, H., Li, H., Wang, G., Wu, Q., Wei, C., Bi, Y., et al. (2013). Direct conversion of fibroblasts to neurons by reprogramming PTB-regulated microRNA circuits. Cell 152, 82-96. DOI
18	Yao, C., Sasaki, H.M., Ueda, T., Tomari, Y., and Tadakuma, H. (2015). Single-molecule analysis of the target cleavage reaction by the Drosophila RNAi enzyme complex. Mol. Cell 59, 125-132. DOI
19	Yekta, S., Shih, I.H., and Bartel, D.P. (2004). MicroRNA-directed cleavage of HOXB8 mRNA. Science 304, 594-596. DOI
20	Zhang, C., and Darnell, R.B. (2011). Mapping in vivo protein-RNA interactions at single-nucleotide resolution from HITS-CLIP data. Nat. Biotechnol. 29, 607-614. DOI
21	Bernstein, E., Kim, S.Y., Carmell, M.A., Murchison, E.P., Alcorn, H., Li, M.Z., Mills, A.A., Elledge, S.J., Anderson, K.V., and Hannon, G.J. (2003). Dicer is essential for mouse development. Nat. Genet. 35, 215-217. DOI
22	Zisoulis, D.G., Lovci, M.T., Wilbert, M.L., Hutt, K.R., Liang, T.Y., Pasquinelli, A.E., and Yeo, G.W. (2010). Comprehensive discovery of endogenous Argonaute binding sites in Caenorhabditis elegans. Nat. Struct Mol. Biol. 17, 173-179. DOI
23	Agarwal, V., Bell, G.W., Nam, J.W., and Bartel, D.P. (2015). Predicting effective microRNA target sites in mammalian mRNAs. eLife 4.
24	Ambros, V. (2004). The functions of animal microRNAs. Nature 431, 350-355. DOI
25	Baek, D., Villen, J., Shin, C., Camargo, F.D., Gygi, S.P., and Bartel, D.P. (2008). The impact of microRNAs on protein output. Nature 455, 64-71. DOI
26	Bartel, D.P. (2009). MicroRNAs: target recognition and regulatory functions. Cell 136, 215-233. DOI
27	Boudreau, R.L., Jiang, P., Gilmore, B.L., Spengler, R.M., Tirabassi, R., Nelson, J.A., Ross, C.A., Xing, Y., and Davidson, B.L. (2014). Transcriptome-wide discovery of microRNA binding sites in human brain. Neuron 81, 294-305. DOI
28	Brennecke, J., Stark, A., Russell, R.B., and Cohen, S.M. (2005). Principles of microRNA-target recognition. PLoS Biol. 3, e85. DOI
29	Brodersen, P., and Voinnet, O. (2009). Revisiting the principles of microRNA target recognition and mode of action. Nat. Rev. Mol. Cell Biol. 10, 141-148.
30	Chandradoss, S.D., Schirle, N.T., Szczepaniak, M., MacRae, I.J., and Joo, C. (2015). A dynamic search process underlies microRNA targeting. Cell 162, 96-107. DOI
31	Chi, S.W., Zang, J.B., Mele, A., and Darnell, R.B. (2009). Argonaute HITS-CLIP decodes microRNA-mRNA interaction maps. Nature 460, 479-486. DOI
32	Chi, S.W., Hannon, G.J., and Darnell, R.B. (2012). An alternative mode of microRNA target recognition. Nat. Struct. Mol. Biol. 19, 321-327. DOI
33	Croce, C.M. (2009). Causes and consequences of microRNA dysregulation in cancer. Nat. Rev. Genet. 10, 704-714. DOI
34	Didiano, D., and Hobert, O. (2006). Perfect seed pairing is not a generally reliable predictor for miRNA-target interactions. Nat. Struct Mol. Biol. 13, 849-851. DOI
35	Easow, G., Teleman, A.A., and Cohen, S.M. (2007). Isolation of microRNA targets by miRNP immunopurification. RNA 13, 1198-1204. DOI
36	Eichhorn, S.W., Guo, H., McGeary, S.E., Rodriguez-Mias, R.A., Shin, C., Baek, D., Hsu, S.H., Ghoshal, K., Villen, J., and Bartel, D.P. (2014). mRNA destabilization is the dominant effect of mammalian microRNAs by the time substantial repression ensues. Mol. Cell 56, 104-115. DOI
37	Elkayam, E., Kuhn, C.D., Tocilj, A., Haase, A.D., Greene, E.M., Hannon, G.J., and Joshua-Tor, L. (2012). The structure of human argonaute-2 in complex with miR-20a. Cell 150, 100-110. DOI
38	Fabian, M.R., Sonenberg, N., and Filipowicz, W. (2010). Regulation of mRNA translation and stability by microRNAs. Ann. Rev. Biochem. 79, 351-379. DOI
39	Filipowicz, W. (2005). RNAi: the nuts and bolts of the RISC machine. Cell 122, 17-20. DOI
40	Friedman, R.C., Farh, K.K., Burge, C.B., and Bartel, D.P. (2009). Most mammalian mRNAs are conserved targets of microRNAs. Genome Res. 19, 92-105.
41	Grimson, A. (2007). MicroRNA targeting specificity in mammals: determinants beyond seed pairing. Mol. Cell 27, 91-105. DOI
42	Grosswendt, S., Filipchyk, A., Manzano, M., Klironomos, F., Schilling, M., Herzog, M., Gottwein, E., and Rajewsky, N. (2014). Unambiguous identification of miRNA:target site interactions by different types of ligation reactions. Mol. Cell 54, 1042-1054. DOI
43	Guo, H., Ingolia, N.T., Weissman, J.S., and Bartel, D.P. (2010). Mammalian microRNAs predominantly act to decrease target mRNA levels. Nature 466, 835-840. DOI
44	Haecker, I., Gay, L.A., Yang, Y., Hu, J., Morse, A.M., McIntyre, L.M., and Renne, R. (2012). Ago HITS-CLIP expands understanding of Kaposi's sarcoma-associated herpesvirus miRNA function in primary effusion lymphomas. PLoS Pathog. 8, e1002884. DOI
45	Hafner, M., Landthaler, M., Burger, L., Khorshid, M., Hausser, J., Berninger, P., Rothballer, A., Ascano, M., Jr., Jungkamp, A.C., Munschauer, M., et al. (2010). Transcriptome-wide identification of RNA-binding protein and microRNA target sites by PAR-CLIP. Cell 141, 129-141. DOI
46	Hammell, M. (2008). mirWIP: microRNA target prediction based on microRNA-containing ribonucleoprotein-enriched transcripts. Nat. Methods 5, 813-819. DOI
47	He, L., and Hannon, G.J. (2004). MicroRNAs: small RNAs with a big role in gene regulation. Nat. Rev. Genet. 5, 522-531. DOI
48	Hebert, S.S., and De Strooper, B. (2009). Alterations of the microRNA network cause neurodegenerative disease. Trend Neurosci. 32, 199-206. DOI
49	Hendrickson, D.G., Hogan, D.J., Herschlag, D., Ferrell, J.E., and Brown, P.O. (2008). Systematic identification of mRNAs recruited to argonaute 2 by specific microRNAs and corresponding changes in transcript abundance. PLoS One 3, e2126. DOI
50	Helwak, A., Kudla, G., Dudnakova, T., and Tollervey, D. (2013). Mapping the human miRNA interactome by CLASH reveals frequent noncanonical binding. Cell 153, 654-665. DOI
51	Jo, M.H., Shin, S., Jung, S.R., Kim, E., Song, J.J., and Hohng, S. (2015). Human argonaute 2 has diverse reaction pathways on target RNAs. Mol. Cell 59, 117-124. DOI
52	John, B., Enright, A.J., Aravin, A., Tuschl, T., Sander, C., and Marks, D.S. (2004). Human MicroRNA targets. PLoS Biol. 2, e363. DOI
53	Kameswaran, V., Bramswig, N.C., McKenna, L.B., Penn, M., Schug, J., Hand, N.J., Chen, Y., Choi, I., Vourekas, A., Won, K.J., et al. (2014). Epigenetic regulation of the DLK1-MEG3 microRNA cluster in human type 2 diabetic islets. Cell Metabol. 19, 135-145. DOI
54	Karginov, F.V. (2007). A biochemical approach to identifying microRNA targets. Proc. Natl. Acad. Sci. USA 104, 19291-19296. DOI
55	Kim, V.N. (2005). Small RNAs: classification, biogenesis, and function. Mol. Cells 19, 1-15. DOI
56	Kim, V.N., Han, J., and Siomi, M.C. (2009). Biogenesis of small RNAs in animals. Nat. Rev. Mol. Cell Biol. 10, 126-139.
57	Kim, K.K., Ham, J., and Chi, S.W. (2013). miRTCat: a comprehensive map of human and mouse microRNA target sites including non-canonical nucleation bulges. Bioinformatics 29, 1898-1899. DOI
58	Konig, J., Zarnack, K., Rot, G., Curk, T., Kayikci, M., Zupan, B., Turner, D.J., Luscombe, N.M., and Ule, J. (2010). iCLIP reveals the function of hnRNP particles in splicing at individual nucleotide resolution. Nat. Struct Mol. Biol. 17, 909-915. DOI
59	Kim, S., Seo, D., Kim, D., Hong, Y., Chang, H., Baek, D., Kim, V.N., Lee, S., and Ahn, K. (2015). Temporal landscape of microRNAmediated host-virus crosstalk during productive human cytomegalovirus infection. Cell Host Microbe 17, 838-851. DOI
60	Kishore, S., Jaskiewicz, L., Burger, L., Hausser, J., Khorshid, M., and Zavolan, M. (2011). A quantitative analysis of CLIP methods for identifying binding sites of RNA-binding proteins. Nat. Methods 8, 559-564. DOI
61	Kozomara, A., and Griffiths-Jones, S. (2014). miRBase: annotating high confidence microRNAs using deep sequencing data. Nucleic Acids Res. 42, D68-73. DOI
62	Krek, A., Grun, D., Poy, M.N., Wolf, R., Rosenberg, L., Epstein, E.J., MacMenamin, P., da Piedade, I., Gunsalus, K.C., Stoffel, M., et al. (2005). Combinatorial microRNA target predictions. Nat. Genet. 37, 495-500. DOI
63	Lal, A., Navarro, F., Maher, C.A., Maliszewski, L.E., Yan, N., O'Day, E., Chowdhury, D., Dykxhoorn, D.M., Tsai, P., Hofmann, O., et al. (2009). miR-24 Inhibits cell proliferation by targeting E2F2, MYC, and other cell-cycle genes via binding to "seedless" 3'UTR microRNA recognition elements. Mol. Cell 35, 610-625. DOI
64	Lee, R.C., Feinbaum, R.L., and Ambros, V. (1993). The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14. Cell 75, 843-854. DOI
65	Lee, H.S., Seok, H., Lee, D.H., Ham, J., Lee, W., Youm, E.M., Yoo, J.S., Lee, Y.S., Jang, E.S., and Chi, S.W. (2015). Abasic pivot substitution harnesses target specificity of RNA interference. Nat. Commun. 6, 10154. DOI
66	Licatalosi, D.D. (2008). HITS-CLIP yields genome-wide insights into brain alternative RNA processing. Nature 456, 464-469. DOI
67	Leung, A.K., Young, A.G., Bhutkar, A., Zheng, G.X., Bosson, A.D., Nielsen, C.B., and Sharp, P.A. (2011). Genome-wide identification of Ago2 binding sites from mouse embryonic stem cells with and without mature microRNAs. Nat. Struct Mol. Biol. 18, 237-244. DOI
68	Lewis, B.P., Shih, I.H., Jones-Rhoades, M.W., Bartel, D.P., and Burge, C.B. (2003). Prediction of mammalian microRNA targets. Cell 115, 787-798. DOI
69	Lewis, B.P., Burge, C.B., and Bartel, D.P. (2005). Conserved seed pairing, often flanked by adenosines, indicates that thousands of human genes are microRNA targets. Cell 120, 15-20. DOI
70	Lim, L.P. (2005). Microarray analysis shows that some microRNAs downregulate large numbers of target mRNAs. Nature 433, 769-773. DOI
71	Liu, J., Carmell, M.A., Rivas, F.V., Marsden, C.G., Thomson, J.M., Song, J.J., Hammond, S.M., Joshua-Tor, L., and Hannon, G.J. (2004). Argonaute2 is the catalytic engine of mammalian RNAi. Science 305, 1437-1441. DOI
72	Loeb, G.B., Khan, A.A., Canner, D., Hiatt, J.B., Shendure, J., Darnell, R.B., Leslie, C.S., and Rudensky, A.Y. (2012). Transcriptome-wide miR-155 binding map reveals widespread noncanonical microRNA targeting. Mol. Cell 48, 760-770. DOI
73	Long, D., Lee, R., Williams, P., Chan, C.Y., Ambros, V., and Ding, Y. (2007). Potent effect of target structure on microRNA function. Nat. Struct Mol. Biol. 14, 287-294. DOI
74	Mili, S., and Steitz, J.A. (2004). Evidence for reassociation of RNAbinding proteins after cell lysis: implications for the interpretation of immunoprecipitation analyses. RNA 10, 1692-1694. DOI
75	Olson, E.N. (2014). MicroRNAs as therapeutic targets and biomarkers of cardiovascular disease. Sci. Translational Med. 6, 239ps233.
76	Moore, M.J., Scheel, T.K., Luna, J.M., Park, C.Y., Fak, J.J., Nishiuchi, E., Rice, C.M., and Darnell, R.B. (2015). miRNA-target chimeras reveal miRNA 3'-end pairing as a major determinant of Argonaute target specificity. Nat. Commun. 6, 8864. DOI
77	Mourelatos, Z. (2008). Small RNAs: the seeds of silence. Nature 455, 44-45. DOI
78	Nakanishi, K., Weinberg, D.E., Bartel, D.P., and Patel, D.J. (2012). Structure of yeast Argonaute with guide RNA. Nature 486, 368-374. DOI
79	Park, C.Y., Choi, Y.S., and McManus, M.T. (2010). Analysis of microRNA knockouts in mice. Hum. Mol. Genet. 19, R169-175. DOI
80	Poy, M.N., Eliasson, L., Krutzfeldt, J., Kuwajima, S., Ma, X., Macdonald, P.E., Pfeffer, S., Tuschl, T., Rajewsky, N., Rorsman, P., et al. (2004). A pancreatic islet-specific microRNA regulates insulin secretion. Nature 432, 226-230. DOI
81	Rajewsky, N. (2006). MicroRNA target predictions in animals. Nat. Genet. 38, S8-S13. DOI
82	Riley, K.J., Rabinowitz, G.S., Yario, T.A., Luna, J.M., Darnell, R.B., and Steitz, J.A. (2012a). EBV and human microRNAs co-target oncogenic and apoptotic viral and human genes during latency. EMBO J. 31, 2207-2221. DOI
83	Riley, K.J., Yario, T.A., and Steitz, J.A. (2012b). Association of Argonaute proteins and microRNAs can occur after cell lysis. RNA 18, 1581-1585. DOI
84	Salomon, W.E., Jolly, S.M., Moore, M.J., Zamore, P.D., and Serebrov, V. (2015). Single-molecule imaging reveals that argonaute reshapes the binding properties of its nucleic acid guides. Cell 162, 84-95. DOI

	Feng Yu. (2017) Nucleic Acids Research Naturally existing isoforms of miR-222 have distinct functions /
4	Marzia Bianchi. (2017) International Journal of Molecular Sciences Coordinated Actions of MicroRNAs with other Epigenetic Factors Regulate Skeletal Muscle Development and Adaptation / 18 (4) , 840
	Fan Yang. (2017) Gene MiR-346 promotes the biological function of breast cancer cells by targeting SRCIN1 and reduces chemosensitivity to docetaxel / 600 , 21
	Heeyoung Seok. (2018) Cellular and Molecular Life Sciences Evaluation and control of miRNA-like off-target repression for RNA interference /
7	Alexander Mildner. (2017) European Journal of Immunology MicroRNA-142 controls thymocyte proliferation / 47 (7) , 1142
	Giuseppe Troiano. (2016) Oral Oncology Circulating miRNAs from blood, plasma or serum as promising clinical biomarkers in oral squamous cell carcinoma: A systematic review of current findings / 63 , 30
2	L. Lampe. (2017) Parasite Immunology The role of microRNAs inAnophelesbiology-an emerging research field / 39 (2) , e12405
	Paola Fuschi. (2019) Antioxidants & Redox Signaling Noncoding RNAs in the Vascular System Response to Oxidative Stress /
10	Xiufeng Zhang. (2017) Proceedings of the National Academy of Sciences Transcriptome-wide microRNA and target dynamics in the fat body during the gonadotrophic cycle ofAedes aegypti / 114 (10) , E1895
	Seung Soo Yoo. (2017) Thoracic Cancer Association between polymorphisms in microRNA target sites and survival in early-stage non-small cell lung cancer /
10	Caterina Catalanotto. (2016) International Journal of Molecular Sciences MicroRNA in Control of Gene Expression: An Overview of Nuclear Functions / 17 (10) , 1712
1	Cecelia Harold. (2016) Virology Journal Epstein-Barr viral microRNAs target caspase 3 / 13 (1)
7	Mengfan Pu. (2017) PLOS Genetics MiR-1254 suppresses HO-1 expression through seed region-dependent silencing and non-seed interaction with TFAP2A transcript to attenuate NSCLC growth / 13 (7) , e1006896
1	Tomas Barta. (2016) Scientific Reports miRNAsong: a web-based tool for generation and testing of miRNA sponge constructs in silico / 6 (1)
	Douglas F. Dluzen. (2017) Oxidative Medicine and Cellular Longevity MicroRNAs Modulate Oxidative Stress in Hypertension through PARP-1 Regulation / 2017 , 1
11	(2018) Clinical and Translational Oncology Re-expression of microRNA-4319 inhibits growth of prostate cancer via Her-2 suppression / 20 (11) , 1400
2	(2018) International Journal of Molecular Sciences Fine-Tuning of Gene Expression by tRNA-Derived Fragments during Abiotic Stress Signal Transduction / 19 (2) , 518
1	(2018) Nutrition & Metabolism MicroRNAs from plants to animals, do they define a new messenger for communication? / 15 (1)
7	(2018) PLOS Computational Biology miRAW: A deep learning-based approach to predict microRNA targets by analyzing whole microRNA transcripts / 14 (7) , e1006185
1420-9071	(2019) Cellular and Molecular Life Sciences Regulatory network of miRNA on its target: coordination between transcriptional and post-transcriptional regulation of gene expression / (1420-9071)
None	(2016) Cancer management and research MicroRNA-142-3p is involved in regulation of <I>MGMT</I> expression in glioblastoma cells / 10 (None) , 775
3	(2018) Cell Proliferation Ginsenoside Rh2 inhibits prostate cancer cell growth through suppression of microRNA-4295 that activates CDKN1A / 51 (3) , e12438
61	(2016) Oncotarget hsa-miR-29c-3p regulates biological function of colorectal cancer by targeting SPARC / 8 (61) , 104508
1	(2017) Molecular cancer A novel mechanism of lncRNA and miRNA interaction: CCAT2 regulates miR-145 expression by suppressing its maturation process in colon cancer cells / 16 (1) , 155
21	(2016) Nucleic acids research CLIPick: a sensitive peak caller for expression-based deconvolution of HITS-CLIP signals / 46 (21) , 11153
None	(2016) Database : the journal of biological databases and curation siAbasic: a comprehensive database for potent siRNA-6Ø sequences without off-target effects / 2018 (None) , bay109
3	(2018) Molecules and cells Post-Transcriptional Control of Tropoelastin in Aortic Smooth Muscle Cells Affects Aortic Dissection Onset / 41 (3) , 198
10	(2016) Cell cycle How RNAi machinery enters the world of telomerase / 18 (10) , 1056
None	(2016) OncoTargets and therapy Bioinformatic analysis of miR-4792 regulates <I>Radix Tetrastigma hemsleyani</I> flavone to inhibit proliferation, invasion, and induce apoptosis of A549 cells / 12 (None) , 1401
1	(2019) Genes Modulation of Bacterial sRNAs Activity by Epigenetic Modifications: Inputs from the Eukaryotic miRNAs / 10 (1) , 22
None	(2016) Frontiers in oncology Upregulation of miR-214 Induced Radioresistance of Osteosarcoma by Targeting PHLDA2 via PI3K/Akt Signaling / 9 (None) , 298
3	(2016) Aging Genetical modification on adipose-derived stem cells facilitates facial nerve regeneration / 11 (3) , 908
1	(2016) Cancer and metastasis reviews Exosomes, metastases, and the miracle of cancer stem cell markers / 38 (1) , 259
7	(2016) RNA biology Systematic evaluation of the microRNAome through miR-CATCHv2.0 identifies positive and negative regulators of <I>BRAF</I>-X1 mRNA / 16 (7) , 865
12	(2016) PLoS computational biology A cell-based probabilistic approach unveils the concerted action of miRNAs / 15 (12) , e1007204
1	(2016) Exrna Current experimental strategies for intracellular target identification of microRNA / 1 (1) , 6
1	(2019) Cellular & molecular biology letters Upregulation of miR-29b-3p protects cardiomyocytes from hypoxia-induced apoptosis by targeting TRAF5 / 24 (1) , 27
1	(2016) Artificial cells, nanomedicine, and biotechnology Long non-coding RNA UCA1 exerts growth modulation by miR-15a in human thyroid cancer TPC-1 cells / 47 (1) , 1815
None	(2020) Frontiers in oncology microRNAs Biogenesis, Functions and Role in Tumor Angiogenesis / 10 (None) , 581007
2	(2016) Current molecular medicine The Role of MicroRNAs in Lung Cancer: Implications for Diagnosis and Therapy / 20 (2) , 90
5	(2020) Journal of cellular physiology miR‐188‐5p suppresses cellular proliferation and migration via IL6ST: A potential noninvasive diagnostic biomarker for breast cancer / 235 (5) , 4890
13	(2020) Aging Hydrostatic pressure induces osteogenic differentiation of adipose-derived mesenchymal stem cells through increasing lncRNA-PAGBC / 12 (13) , 13477
7820	(2020) Nature Position-specific oxidation of miR-1 encodes cardiac hypertrophy / 584 (7820) , 279
6	(2020) Oncology letters miR-421 promotes the viability of A549 lung cancer cells by targeting forkhead box O1 / 20 (6) , 306
1	(2016) Respiratory research 6′-O-galloylpaeoniflorin regulates proliferation and metastasis of non-small cell lung cancer through AMPK/miR-299-5p/ATF2 axis / 21 (1) , 39
None	(2016) OncoTargets and therapy TRPM2-AS Promotes Bladder Cancer by Targeting miR-22-3p and Regulating GINS2 mRNA Expression / 14 (None) , 1219
1	(2021) Bioengineered MicroRNA expression profile and identification of novel microRNA biomarkers for metabolic syndrome / 12 (1) , 3864
None	(2016) BioMed research international Construction and Analysis of Survival-Associated Competing Endogenous RNA Network in Lung Adenocarcinoma / 2021 (None) , 1
None	(2016) Computational and structural biotechnology journal Prediction methods for microRNA targets in bilaterian animals: Toward a better understanding by biologists / 19 (None) , 5811
None	(2016) Molecular therapy. Nucleic acids AGO-accessible anticancer siRNAs designed with synergistic miRNA-like activity / 23 (None) , 1172
3	(2016) Journal of personalized medicine The Importance of Epigenetics in Diagnostics and Treatment of Major Depressive Disorder / 11 (3) , 167
2	(2016) Computational and systems oncology Role of microRNAs in oncogenesis: Insights from computational and systems‐level modeling approaches / 1 (2) , None
6	(2016) The FASEB journal : official publication of the Federation of American Societies for Experimental Biology Mechanical overload‐induced muscle‐derived extracellular vesicles promote adipose tissue lipolysis / 35 (6) , None
11	(2021) British journal of pharmacology : BJP Eating microRNAs: pharmacological opportunities for cross‐kingdom regulation and implications in host gene and gut microbiota modulation / 178 (11) , 2218
28	(2016) Environmental science and pollution research international MicroRNAs’ role in the environment-related non-communicable diseases and link to multidrug resistance, regulation, or alteration / 28 (28) , 36984
8	(2016) Biomolecules MicroRNAs and Stem-like Properties: The Complex Regulation Underlying Stemness Maintenance and Cancer Development / 11 (8) , 1074
5	(2016) Pigment cell & melanoma research Human <I>TYRP1</I>: Two functions for a single gene? / 34 (5) , 836
9	(2016) Canadian journal of physiology and pharmacology MicroRNA regulation of vascular smooth muscle cells and its significance in cardiovascular diseases / 99 (9) , 827
6	(2021) Insect molecular biology Functional analysis of a putative <I>Bombyx mori</I> cypovirus miRNA BmCPV‐miR‐10 and its effect on virus replication / 30 (6) , 552
1	(2016) Genome biology Crosstalk between codon optimality and <I>cis</I> -regulatory elements dictates mRNA stability / 22 (1) , 14
23	(2016) International journal of molecular sciences Overexpression of an Osa-miR162a Derivative in Rice Confers Cross-Kingdom RNA Interference-Mediated Brown Planthopper Resistance without Perturbing Host Development / 22 (23) , 12652