MicroRNAs in the regulation of Wnt/β-Catenin, NF-kB, PI3K/AKT, STAT3, p53, and Hedgehog pathway
Background and aim: There are two significant challenges in cancer treatment: malignancy and resistance to anti-cancer drugs. As a result, a thorough understanding of cancer etiology is essential for developing new cancer treatments. There is a crucial role for micro-RNAs in physiological processes as well as pathological processes. Cancer pathogenesis is strongly influenced by miRNAs, which play a crucial role in neoplastic disease pathophysiology. They can be used to diagnose, prognosticate, and treat a wide range of cancers. Also, they play an important role in metastasis and resistance to treatment and the stamens of cancer stem cells by regulating several signaling networks. A better understanding of the miRNAs that play a role in cancer's signaling pathways could lead to new cancer diagnostic, prognostic, and treatment options. This study focuses on miRNAs, which play a vital part in regulating cancer-related signaling networks and pathogenic signaling pathways in cancer.
Relevance for patients: This study highlights the relevance of microRNAs (miRNAs) in cancer, as they have a significant role in cancer development, metastasis, treatment resistance, and cancer stem cells. Understanding the role of miRNAs in cancer signaling pathways could lead to improved diagnostics, prognostics, and treatment options for patients.
1 Ming H, Li B, Zhou L, Goel A, Huang C. Long non-coding rnas and cancer metastasis: Molecular basis and therapeutic implications. Biochimica et Biophysica Acta (BBA)-Reviews on Cancer 2021;1875:188519.
2 Hanahan D. Hallmarks of cancer: New dimensions. Cancer Discovery 2022;12:31-46.
3 Tensen CP, Quint KD, Vermeer MH. Genetic and epigenetic insights into cutaneous t-cell lymphoma. Blood, The Journal of the American Society of Hematology 2022;139:15-33.
4 Pei Y, Zhang H, Lu K, Tang X, Li J, Zhang E, Zhang J, Huang Y, Yang Z, Lu Z. Circular rna circrna_0067934 promotes glioma development by modulating the microrna mir-7/wnt/β-catenin axis. Bioengineered 2022;13:5792-5802.
5 Kim SL, Shin MW, Seo SY, Kim SW. Lipocalin 2 potentially contributes to tumorigenesis from colitis via il-6/stat3/nf-kb signaling pathway. Bioscience Reports 2022
6 Ko E-B, Jang Y-G, Kim C-W, Go R-E, Lee HK, Choi K-C. Gallic acid hindered lung cancer progression by inducing cell cycle arrest and apoptosis in a549 lung cancer cells via pi3k/akt pathway. Biomolecules & Therapeutics 2022;30:151.
7 Lu X, An L, Fan G, Zang L, Huang W, Li J, Liu J, Ge W, Huang Y, Xu J. Egfr signaling promotes nuclear translocation of plasma membrane protein tspan8 to enhance tumor progression via stat3- mediated transcription. Cell Research 2022;32:359-374.
8 Ou A, Zhao X, Lu Z. The potential roles of p53 signaling reactivation in pancreatic cancer therapy. Biochimica et Biophysica Acta (BBA)-Reviews on Cancer 2022;1877:188662.
9 Zhu Y, Peng X, Zhou Q, Tan L, Zhang C, Lin S, Long M. Mettl3-mediated m6a modification of steap2 mrna inhibits papillary thyroid cancer progress by blocking the hedgehog signaling pathway and epithelial-to-mesenchymal transition. Cell death & disease 2022;13:1-11.
10 García-Padilla C, Dueñas Á, García-López V, Aránega A, Franco D, Garcia-Martínez V, LópezSánchez C. Molecular mechanisms of lncrnas in the dependent regulation of cancer and their potential therapeutic use. International Journal of Molecular Sciences 2022;23:764.
11 Arghiani N, Shah K. Modulating micrornas in cancer: Next-generation therapies. Cancer Biology & Medicine 2022;19:289.
12 Sanchez Calle A, Kawamura Y, Yamamoto Y, Takeshita F, Ochiya T. Emerging roles of long non‐ coding rna in cancer. Cancer science 2018;109:2093-2100.
13 Bhan A, Soleimani M, Mandal SS. Long noncoding rna and cancer: A new paradigm. Cancer research 2017;77:3965-3981.
14 Alexovič M, Lindner JR, Bober P, Longuespée R, Sabo J, Davalieva K. Human peripheral blood mononuclear cells: A review of recent proteomic applications. Proteomics 2022;22:2200026.
15 Calin GA, Dumitru CD, Shimizu M, Bichi R, Zupo S, Noch E, Aldler H, Rattan S, Keating M, Rai K. Frequent deletions and down-regulation of micro-rna genes mir15 and mir16 at 13q14 in chronic lymphocytic leukemia. Proceedings of the national academy of sciences 2002;99:15524-15529.
16 Witek Ł, Janikowski T, Gabriel I, Bodzek P, Olejek A. Analysis of microrna regulating cell cyclerelated tumor suppressor genes in endometrial cancer patients. Human Cell 2021;34:564-569.
17 Liu X, Ma R, Yi B, Riker AI, Xi Y. Micrornas are involved in the development and progression of gastric cancer. Acta Pharmacologica Sinica 2021;42:1018-1026.
18 Zhang M, Du X. Noncoding rnas in gastric cancer: Research progress and prospects. World J Gastroenterol 2016;22:6610-6618.
19 Xu X, Zhang M, Xu F, Jiang S. Wnt signaling in breast cancer: Biological mechanisms, challenges and opportunities. Molecular Cancer 2020;19:1-35.
20 Flores-Hernández E, Velázquez DM, Castañeda-Patlán MC, Fuentes-García G, Fonseca-Camarillo G, Yamamoto-Furusho JK, Romero-Avila MT, García-Sáinz JA, Robles-Flores M. Canonical and noncanonical wnt signaling are simultaneously activated by wnts in colon cancer cells. Cellular signalling 2020;72:109636.
21 He S, Tang S. Wnt/β-catenin signaling in the development of liver cancers. Biomedicine & Pharmacotherapy 2020;132:110851.
22 Koushyar S, Powell AG, Vincan E, Phesse TJ. Targeting wnt signaling for the treatment of gastric cancer. International Journal of Molecular Sciences 2020;21:3927.
23 Denli AM, Tops BB, Plasterk RH, Ketting RF, Hannon GJ. Processing of primary micrornas by the microprocessor complex. Nature 2004;432:231-235.
24 Lee Y, Ahn C, Han J, Choi H, Kim J, Yim J, Lee J, Provost P, Rådmark O, Kim S. The nuclear rnase iii drosha initiates microrna processing. Nature 2003;425:415-419.
25 Bohnsack MT, Czaplinski K, Görlich D. Exportin 5 is a rangtp-dependent dsrna-binding protein that mediates nuclear export of pre-mirnas. Rna 2004;10:185-191.
26 Bartel DP. Micrornas: Genomics, biogenesis, mechanism, and function. cell 2004;116:281-297.
27 Ørom UA, Nielsen FC, Lund AH. Microrna-10a binds the 5′ utr of ribosomal protein mrnas and enhances their translation. Molecular cell 2008;30:460-471.
28 Qin W, Shi Y, Zhao B, Yao C, Jin L, Ma J, Jin Y. Mir-24 regulates apoptosis by targeting the open reading frame (orf) region of faf1 in cancer cells. PloS one 2010;5:e9429.
29 Cummins J, Velculescu V. Implications of micro-rna profiling for cancer diagnosis. Oncogene 2006;25:6220-6227.
30 Takamizawa J, Konishi H, Yanagisawa K, Tomida S, Osada H, Endoh H, Harano T, Yatabe Y, Nagino M, Nimura Y. Reduced expression of the let-7 micrornas in human lung cancers in association with shortened postoperative survival. Cancer research 2004;64:3753-3756.
31 Tsang JS, Ebert MS, van Oudenaarden A. Genome-wide dissection of microrna functions and cotargeting networks using gene set signatures. Molecular cell 2010;38:140-153.
32 Iorio MV, Croce CM. Microrna dysregulation in cancer: Diagnostics, monitoring and therapeutics. A comprehensive review. EMBO molecular medicine 2012;4:143-159.
33 Izumchenko E, Chang X, Michailidi C, Kagohara L, Ravi R, Paz K, Brait M, Hoque MO, Ling S, Bedi A. The tgfβ–mir200–mig6 pathway orchestrates the emt-associated kinase switch that induces resistance to egfr inhibitors. Cancer research 2014;74:3995-4005.
34 Brown RA, Epis MR, Horsham JL, Kabir TD, Richardson KL, Leedman PJ. Total rna extraction from tissues for microrna and target gene expression analysis: Not all kits are created equal. BMC biotechnology 2018;18:1-11.
35 Qing T, Yu Y, Du T, Shi L. Mrna enrichment protocols determine the quantification characteristics of external rna spike-in controls in rna-seq studies. Science China life sciences 2013;56:134-142.
36 Peterson SM, Freeman JL. Rna isolation from embryonic zebrafish and cdna synthesis for gene expression analysis. JoVE (Journal of Visualized Experiments) 2009:e1470.
37 VanGuilder HD, Vrana KE, Freeman WM. Twenty-five years of quantitative pcr for gene expression analysis. Biotechniques 2008;44:619-626.
38 Rio DC. Reverse transcription–polymerase chain reaction. Cold Spring Harbor Protocols 2014;2014:pdb. prot080887.
39 Ozsolak F, Milos PM. Rna sequencing: Advances, challenges and opportunities. Nature reviews genetics 2011;12:87-98.
40 Sealfon SC, Chu TT. Rna and DNA microarrays. Biological Microarrays: Methods and Protocols 2011:3-34.
41 Lehmann R, Tautz D. In situ hybridization to rna. Methods in cell biology 1994;44:575-598.
42 Koscianska E, Starega-Roslan J, Sznajder LJ, Olejniczak M, Galka-Marciniak P, Krzyzosiak WJ. Northern blotting analysis of micrornas, their precursors and rna interference triggers. BMC molecular biology 2011;12:1-7.
43 Li HL, Liang S, Cui JH, Han GY. Targeting of gsk-3β by mir-214 to facilitate gastric cancer cell proliferation and decrease of cell apoptosis. Eur Rev Med Pharmacol Sci 2018;22:127-134.
44 Fan D, Ren B, Yang X, Liu J, Zhang Z. Upregulation of mir-501-5p activates the wnt/β-catenin signaling pathway and enhances stem cell-like phenotype in gastric cancer. J Exp Clin Cancer Res 2016;35:177.
45 Willert K, Nusse R. Wnt proteins. Cold Spring Harb Perspect Biol 2012;4:a007864.
46 Alok A, Lei Z, Jagannathan NS, Kaur S, Harmston N, Rozen SG, Tucker-Kellogg L, Virshup DM. Wnt proteins synergize to activate β-catenin signaling. J Cell Sci 2017;130:1532-1544.
47 Cha YH, Kim NH, Park C, Lee I, Kim HS, Yook JI. Mirna-34 intrinsically links p53 tumor suppressor and wnt signaling. Cell cycle 2012;11:1273-1281.
48 Li Y, Yan X, Shi J, He Y, Xu J, Lin L, Chen W, Lin X, Lin X. Aberrantly expressed mir-188-5p promotes gastric cancer metastasis by activating wnt/β-catenin signaling. BMC Cancer 2019;19:505.
49 Xu K, Zhao YC. Mef2d/wnt/β-catenin pathway regulates the proliferation of gastric cancer cells and is regulated by microrna-19. Tumour Biol 2016;37:9059-9069.
50 Fang Z, Zhong M, Wang Y, Yuan X, Guo H, Yao Y, Feng M, Chen J, Xiong J, Xiang X. Mir‑381 and mir‑489 suppress cell proliferation and invasion by targeting cul4b via the wnt/β‑catenin pathway in gastric cancer. Int J Oncol 2019;54:733-743.
51 Plotnikova O, Baranova A, Skoblov M. Comprehensive analysis of human microrna–mrna interactome. Frontiers in genetics 2019:933.
52 Niu T, Liu N, Zhao M, Xie G, Zhang L, Li J, Pei Y-F, Shen H, Fu X, He H. Identification of a novel fgfrl1 microrna target site polymorphism for bone mineral density in meta-analyses of genome-wide association studies. Human molecular genetics 2015;24:4710-4727.
53 Jiang L, Lin C, Song L, Wu J, Chen B, Ying Z, Fang L, Yan X, He M, Li J. Microrna-30e* promotes human glioma cell invasiveness in an orthotopic xenotransplantation model by disrupting the nf-κb/iκbα negative feedback loop. The Journal of clinical investigation 2012;122:33-47.
54 Guo Z, Pan F, Peng L, Tian S, Jiao J, Liao L, Lu C, Zhai G, Wu Z, Dong H. Systematic proteome and lysine succinylome analysis reveals enhanced cell migration by hyposuccinylation in esophageal squamous cell carcinoma. Molecular & Cellular Proteomics 2021;20
55 Gong H, Song L, Lin C, Liu A, Lin X, Wu J, Li M, Li J. Downregulation of mir-138 sustains nf-κb activation and promotes lipid raft formation in esophageal squamous cell carcinoma. Clinical Cancer Research 2013;19:1083-1093.
56 Hu X, Wu X. Ubiquitin proteasome system regulates biological particles interaction in particle disease (pd) via nf-kb signaling. Journal of Cellular Signaling 2020;1
57 Wertz IE, Dixit VM. Signaling to nf-κb: Regulation by ubiquitination. Cold Spring Harbor perspectives in biology 2010;2:a003350.
58 Song L, Lin C, Gong H, Wang C, Liu L, Wu J, Tao S, Hu B, Cheng S-Y, Li M. Mir-486 sustains nf-κb activity by disrupting multiple nf-κb-negative feedback loops. Cell research 2013;23:274-289.
59 Iwai K, Fujita H, Sasaki Y. Linear ubiquitin chains: Nf-κb signalling, cell death and beyond. Nature reviews Molecular cell biology 2014;15:503-508.
60 Song L, Liu L, Wu Z, Li Y, Ying Z, Lin C, Wu J, Hu B, Cheng S-Y, Li M. Tgf-β induces mir-182 to sustain nf-κb activation in glioma subsets. The Journal of clinical investigation 2012;122:3563-3578.
61 Wang X, Wang H, Zhang X, Bi C, McKeithan TW, Huang X, Meng B, Chan WC, Vose JM, Zhang H. Mir-17~ 92 promotes progression of abc-dlbcl lymphoma via regulation of canonical nf-kb signaling. 2021
62 Gao Y, Han T, Han C, Sun H, Yang X, Zhang D, Ni X. Propofol regulates the tlr4/nf-κb pathway through mirna-155 to protect colorectal cancer intestinal barrier. Inflammation 2021:1-13.
63 Luo X, Dong J, He X, Shen L, Long C, Liu F, Liu X, Lin T, He D, Wei G. Mir-155-5p exerts tumor-suppressing functions in wilms tumor by targeting igf2 via the pi3k signaling pathway. Biomedicine & Pharmacotherapy 2020;125:109880.
64 Jia L, Luo S, Ren X, Li Y, Hu J, Liu B, Zhao L, Shan Y, Zhou H. Mir-182 and mir-135b mediate the tumorigenesis and invasiveness of colorectal cancer cells via targeting st6galnac2 and pi3k/akt pathway. Digestive diseases and sciences 2017;62:3447-3459.
65 Li X, Zhang X, Zhang Q, Lin R. Mir-182 contributes to cell proliferation, invasion and tumor growth in colorectal cancer by targeting dab2ip. The international journal of biochemistry & cell biology 2019;111:27-36.
66 Xu J, Zhao J, Jiang M, Yang L, Sun M, Wang H. Mir-193 promotes cell proliferation and invasion by ing5/pi3k/akt pathway of triple-negative breast cancer. Eur Rev Med Pharmacol Sci 2020;24:3122-3129.
67 Siddiqui WA, Ahad A, Ahsan H. The mystery of bcl2 family: Bcl-2 proteins and apoptosis: An update. Arch Toxicol 2015;89:289-317.
68 Yang ZY, Wang Y, Liu Q, Wu M. Microrna cluster mc-let-7a-1~let-7d promotes autophagy and apoptosis of glioma cells by down-regulating stat3. CNS Neurosci Ther 2020;26:319-331.
69 Yu-Ju Wu C, Chen C-H, Lin C-Y, Feng L-Y, Lin Y-C, Wei K-C, Huang C-Y, Fang J-Y, Chen P-Y. Ccl5 of glioma-associated microglia/macrophages regulates glioma migration and invasion via calcium-dependent matrix metalloproteinase 2. Neuro-oncology 2020;22:253-266.
70 Peng T, Zhou L, Zuo L, Luan Y. Mir-506 functions as a tumor suppressor in glioma by targeting stat3. Oncol Rep 2016;35:1057-1064.
71 Liu H-W, Lee PM, Bamodu OA, Su Y-K, Fong I-H, Yeh C-T, Chien M-H, Kan I, Lin C-M. Enhanced hsa-mir-181d/p-stat3 and hsa-mir-181d/p-stat5a ratios mediate the anticancer effect of garcinol in stat3/5a-addicted glioblastoma. Cancers 2019;11:1888.
72 Choi S, Yu Y, Grimmer MR, Wahl M, Chang SM, Costello JF. Temozolomide-associated hypermutation in gliomas. Neuro Oncol 2018;20:1300-1309.
73 Xu JX, Yang Y, Zhang X, Luan XP. Microrna-29b promotes cell sensitivity to temozolomide by targeting stat3 in glioma. Eur Rev Med Pharmacol Sci 2020;24:1922-1931.
74 Hong L, Ya-Wei L, Hai W, Qiang Z, Jun-Jie L, Huang A, Song-Tao Q, Yun-Tao L. Mir-519a functions as a tumor suppressor in glioma by targeting the oncogenic stat3 pathway. J Neurooncol 2016;128:35-45.
75 Li H, Chen L, Li JJ, Zhou Q, Huang A, Liu WW, Wang K, Gao L, Qi ST, Lu YT. Mir-519a enhances chemosensitivity and promotes autophagy in glioblastoma by targeting stat3/bcl2 signaling pathway. J Hematol Oncol 2018;11:70.
76 Wei J, Wang F, Kong LY, Xu S, Doucette T, Ferguson SD, Yang Y, McEnery K, Jethwa K, Gjyshi O, Qiao W, Levine NB, Lang FF, Rao G, Fuller GN, Calin GA, Heimberger AB. Mir-124 inhibits stat3 signaling to enhance t cell-mediated immune clearance of glioma. Cancer Res 2013;73:3913-3926.
77 Wu Y, Wan X, Zhao X, Song Z, Xu Z, Tao Y, Sun C. Microrna-143 suppresses the proliferation and metastasis of human gastric cancer cells via modulation of stat3 expression. American journal of translational research 2020;12:867.
78 Liu Y-B, Wang Y, Zhang M-D, Yue W, Sun C-N. Microrna-29a functions as a tumor suppressor through targeting stat3 in laryngeal squamous cell carcinoma. Experimental and Molecular Pathology 2020;116:104521.
79 Roshani Asl E, Rasmi Y, Baradaran B. Microrna‐124‐3p suppresses pd‐l1 expression and inhibits tumorigenesis of colorectal cancer cells via modulating stat3 signaling. Journal of Cellular Physiology 2021.
80 Tian K, Liu W, Zhang J, Fan X, Liu J, Zhao N, Yao C, Miao G. Microrna-125b exerts antitumor functions in cutaneous squamous cell carcinoma by targeting the stat3 pathway. Cellular & molecular biology letters 2020;25:1-12.
81 Yan X-L, Luo Q-Y, Zhou S-N, Pan W-T, Zhang L, Yang D-J, Qiu M-Z. Microrna-375 reverses the expression of pd-l1 by inactivating the jak2/stat3 signaling pathways in gastric cancer. Clinics and Research in Hepatology and Gastroenterology 2021;45:101574.
82 Li C, Li H, Zhang P, Yu L-J, Huang T-M, Song X, Kong Q-Y, Dong J-L, Li P-N, Liu J. Shp2, socs3 and pias3 expression patterns in medulloblastomas: Relevance to stat3 activation and resveratrol-suppressed stat3 signaling. Nutrients 2017;9:3.
83 Xu CH, Liu Y, Xiao LM, Chen LK, Zheng SY, Zeng EM, Li DH, Li YP. Silencing microrna-221/222 cluster suppresses glioblastoma angiogenesis by suppressor of cytokine signaling-3-dependent jak/stat pathway. J Cell Physiol 2019;234:22272-22284.
84 Che S, Sun T, Wang J, Jiao Y, Wang C, Meng Q, Qi W, Yan Z. Mir-30 overexpression promotes glioma stem cells by regulating jak/stat3 signaling pathway. Tumour Biol 2015;36:6805-6811.
85 Jiao J, Zhang R, Li Z, Yin Y, Fang X, Ding X, Cai Y, Yang S, Mu H, Zong D, Chen Y, Zhang Y, Zou J, Shao J, Huang Z. Nuclear smad6 promotes gliomagenesis by negatively regulating pias3-mediated stat3 inhibition. Nat Commun 2018;9:2504.
86 Shi L, Wan Y, Sun G, Zhang S, Wang Z, Zeng Y. Mir-125b inhibitor may enhance the invasion-prevention activity of temozolomide in glioblastoma stem cells by targeting pias3. BioDrugs 2014;28:41-54.
87 Song Z-B, Yang H-P, Xu A-Q, Zhan Z-M, Song Y, Li Z-Y. Connective tissue growth factor as an unfavorable prognostic marker promotes the proliferation, migration, and invasion of gliomas. Chinese medical journal 2020;133:670.
88 Zhang P, Chen FZ, Jia QB, Hu DF. Upregulation of microrna-133a and downregulation of connective tissue growth factor suppress cell proliferation, migration, and invasion in human glioma through the jak/stat signaling pathway. IUBMB Life 2019;71:1857-1875.
89 Zhang Z, Gong Q, Li M, Xu J, Zheng Y, Ge P, Chi G. Microrna-124 inhibits the proliferation of c6 glioma cells by targeting smad4. Int J Mol Med 2017;40:1226-1234.
90 Cai Q, Zhu A, Gong L. Exosomes of glioma cells deliver mir-148a to promote proliferation and metastasis of glioblastoma via targeting cadm1. Bull Cancer 2018;105:643-651.
91 Saito K, Ohta S, Kawakami Y, Yoshida K, Toda M. Functional analysis of kif20a, a potential immunotherapeutic target for glioma. J Neurooncol 2017;132:63-74.
92 Tang J, Xu J, Zhi Z, Wang X, Wang Y, Zhou Y, Chen R. Mir-876-3p targets kif20a to block jak2/stat3 pathway in glioma. Am J Transl Res 2019;11:4957-4966.
93 Cheng J, Meng J, Zhu L, Peng Y. Exosomal noncoding rnas in glioma: Biological functions and potential clinical applications. Mol Cancer 2020;19:66.
94 Qian M, Wang S, Guo X, Wang J, Zhang Z, Qiu W, Gao X, Chen Z, Xu J, Zhao R, Xue H, Li G. Hypoxic glioma-derived exosomes deliver microrna-1246 to induce m2 macrophage polarization by targeting terf2ip via the stat3 and nf-κb pathways. Oncogene 2020;39:428-442.
95 Network CGAR. Comprehensive genomic characterization defines human glioblastoma genes and core pathways. Nature 2008;455:1061.
96 Le MT, Teh C, Shyh-Chang N, Xie H, Zhou B, Korzh V, Lodish HF, Lim B. Microrna-125b is a novel negative regulator of p53. Genes & development 2009;23:862-876.
97 Le MT, Shyh-Chang N, Khaw SL, Chin L, Teh C, Tay J, O'Day E, Korzh V, Yang H, Lal A. Conserved regulation of p53 network dosage by microrna–125b occurs through evolving mirna–target gene pairs. PLoS genetics 2011;7:e1002242.
98 Nishida N, Yokobori T, Mimori K, Sudo T, Tanaka F, Shibata K, Ishii H, Doki Y, Kuwano H, Mori M. Microrna mir-125b is a prognostic marker in human colorectal cancer. International journal of oncology 2011;38:1437-1443.
99 Enomoto Y, Kitaura J, Hatakeyama K, Watanuki J, Akasaka T, Kato N, Shimanuki M, Nishimura K, Takahashi M, Taniwaki M. Eμ/mir-125b transgenic mice develop lethal b-cell malignancies. Leukemia 2011;25:1849-1856.
100 Zhang Y, Yan L-X, Wu Q-N, Du Z-M, Chen J, Liao D-Z, Huang M-Y, Hou J-H, Wu Q-L, Zeng M-S. Mir-125b is methylated and functions as a tumor suppressor by regulating the ets1 proto-oncogene in human invasive breast cancer. Cancer research 2011;71:3552-3562.
101 Yamakuchi M, Ferlito M, Lowenstein CJ. Mir-34a repression of sirt1 regulates apoptosis. Proceedings of the National Academy of Sciences 2008;105:13421-13426.
102 Eades G, Yao Y, Yang M, Zhang Y, Chumsri S, Zhou Q. Mir-200a regulates sirt1 expression and epithelial to mesenchymal transition (emt)-like transformation in mammary epithelial cells. Journal of Biological Chemistry 2011;286:25992-26002.
103 Kaller M, Liffers S-T, Oeljeklaus S, Kuhlmann K, Röh S, Hoffmann R, Warscheid B, Hermeking H. Genome-wide characterization of mir-34a induced changes in protein and mrna expression by a combined pulsed silac and microarray analysis. Molecular & Cellular Proteomics 2011;10.
104 Chen Q-R, Yu L-R, Tsang P, Wei JS, Song YK, Cheuk A, Chung J-Y, Hewitt SM, Veenstra TD, Khan J. Systematic proteome analysis identifies transcription factor yy1 as a direct target of mir-34a. Journal of proteome research 2011;10:479-487.
105 Bouscary D. Rational for targeting the hedgehog signalling pathway in acute myeloid leukemia with flt3 mutation. Ann Transl Med 2016;4:S53.
106 Li J, Zhang Q, Fan X, Mo W, Dai W, Feng J, Wu L, Liu T, Li S, Xu S, Wang W, Lu X, Yu Q, Chen K, Xia Y, Lu J, Zhou Y, Xu L, Guo C. The long noncoding rna tug1 acts as a competing endogenous rna to regulate the hedgehog pathway by targeting mir-132 in hepatocellular carcinoma. Oncotarget 2017;8:65932-65945.
107 Song JH, Tieu AH, Cheng Y, Ma K, Akshintala VS, Simsek C, Prasath V, Shin EJ, Ngamruengphong S, Khashab MA. Novel long noncoding rna mir205hg functions as an esophageal tumor-suppressive hedgehog inhibitor. Cancers 2021;13:1707.