Combinatorial Chemistry & High Throughput ScreeningCombinatorial Chemistry & High Throughput ScreeningCombinatorial Chemistry & High Throughput Screening1386-20731875-5402Bentham Science64374010.2174/1386207326666230602090848ChemistryResearch ArticleOver-expression of microRNA-145 Elevating Autophagy Activities via Downregulating FRS2 ExpressionTianKeinfo@benthamscience.netDengBininfo@benthamscience.netHanXiaodonginfo@benthamscience.netZhengHaiyiinfo@benthamscience.netLinTaoinfo@benthamscience.netWangZhimenginfo@benthamscience.netZhangYuanmininfo@benthamscience.netWangGuodonginfo@benthamscience.netDepartment of Orthopedics and Joint, Affiiated Hospital of Jining Medical UniversityDepartment of Orthopedics, Affiliated Hospital of Jining Medical University0101202427112713507012025Copyright ©; 2024, Bentham Science Publishers2024Bentham Science Publishershttps://rjpbr.com/1386-2073/article/view/643740

Objectives:Osteoarthritis (OA) is one of the most common chronic and progressive joint diseases characterized by cartilage degeneration and chondrocyte death. In this study, we aimed to identify the modulation effect of miR-145 on chondrocytes' autophagy during the development of OA.

Background:Osteoarthritis (OA) is one of the most prevalent types of chronic and progressive joint disorder with the symptoms of joint pain and stiffness, and it leads to disability at the end stage. In recent years, microRNA-145 (miR-145) has been found to activate autophagy in various cell types, including mesenchymal stem cells, cardiomyocytes, and osteosarcoma cells. However, it is unknown whether miR-145 regulates the progression of OA by influencing chondrocyte autophagy.

Methods:Before investigating the regulatory effect of miR-145 on the autophagic activity of chondrocytes, the expression of miR-145 in human joint samples was analyzed. The targeting relationship between miR-145 and FRS2 was detected by dual luciferase assay. The effect of FRS2 and miR-145 on the autophagic activity of chondrocytes was observed by bidirectional expression of FRS2 and miR-145.

Results:The miR-145 expression and LC3-II/LC3-I ratio were significantly decreased and the SQSTM1 expression was increased in OA patients. The miR-145 overexpression in C20A4 cells increased LC3-II/LC3-I ratio, decreased SQSTM1 expression, and was positively correlated with autophagic activity. Under oxidative stress, miR-145 overexpression significantly improved chondrocyte viability through autophagy stimulation. FRS2 is a potential target of miR-145 via a binding sequence within its 3’ UTR. FRS2 acts as the downstream mediator of miR-145 to suppress autophagy through activating PI3K/Akt/mTOR pathways.

Conclusion:The miR-145 acts as a protective factor against chondrocytes by regulating miRFRS2- autophagy axis. The decrease of miR-145 in articular synovial fluid may turn out to be an important marker for early diagnosis of OA, and modulation of miR-145 may represent a promising therapeutic strategy for OA.

OsteoarthritismiR-145autophagyFRS2PI3K/Akt/Mtorchondrocytes.Vos, T.; Allen, C.; Arora, M.; Barber, R.M.; Bhutta, Z.A.; Brown, A.; Carter, A.; Casey, D.C.; Charlson, F.J.; Chen, A.Z.; Coggeshall, M.; Cornaby, L.; Dandona, L.; Dicker, D.J.; Dilegge, T.; Erskine, H.E.; Ferrari, A.J.; Fitzmaurice, C.; Fleming, T.; Forouzanfar, M.H.; Fullman, N.; Gething, P.W.; Goldberg, E.M.; Graetz, N.; Haagsma, J.A.; Hay, S.I.; Johnson, C.O.; Kassebaum, N.J.; Kawashima, T.; Kemmer, L.; Khalil, I.A.; Kinfu, Y.; Kyu, H.H.; Leung, J.; Liang, X.; Lim, S.S.; Lopez, A.D.; Lozano, R.; Marczak, L.; Mensah, G.A.; Mokdad, A.H.; Naghavi, M.; Nguyen, G.; Nsoesie, E.; Olsen, H.; Pigott, D.M.; Pinho, C.; Rankin, Z.; Reinig, N.; Salomon, J.A.; Sandar, L.; Smith, A.; Stanaway, J.; Steiner, C.; Teeple, S.; Thomas, B.A.; Troeger, C.; Wagner, J.A.; Wang, H.; Wanga, V.; Whiteford, H.A.; Zoeckler, L.; Abajobir, A.A.; Abate, K.H.; Abbafati, C.; Abbas, K.M.; Abd-Allah, F.; Abraham, B.; Abubakar, I.; Abu-Raddad, L.J.; Abu-Rmeileh, N.M.E.; Ackerman, I.N.; Adebiyi, A.O.; Ademi, Z.; Adou, A.K.; Afanvi, K.A.; Agardh, E.E.; Agarwal, A.; Kiadaliri, A.A.; Ahmadieh, H.; Ajala, O.N.; Akinyemi, R.O.; Akseer, N.; Al-Aly, Z.; Alam, K.; Alam, N.K.M.; Aldhahri, S.F.; Alegretti, M.A.; Alemu, Z.A.; Alexander, L.T.; Alhabib, S.; Ali, R.; Alkerwi, A.; Alla, F.; Allebeck, P.; Al-Raddadi, R.; Alsharif, U.; Altirkawi, K.A.; Alvis-Guzman, N.; Amare, A.T.; Amberbir, A.; Amini, H.; Ammar, W.; Amrock, S.M.; Andersen, H.H.; Anderson, G.M.; Anderson, B.O.; Antonio, C.A.T.; Aregay, A.F.; Ärnlöv, J.; Artaman, A.; Asayesh, H.; Assadi, R.; Atique, S.; Avokpaho, E.F.G.A.; Awasthi, A.; Quintanilla, B.P.A.; Azzopardi, P.; Bacha, U.; Badawi, A.; Balakrishnan, K.; Banerjee, A.; Barac, A.; Barker-Collo, S.L.; Bärnighausen, T.; Barregard, L.; Barrero, L.H.; Basu, A.; Bazargan-Hejazi, S.; Beghi, E.; Bell, B.; Bell, M.L.; Bennett, D.A.; Bensenor, I.M.; Benzian, H.; Berhane, A.; Bernabé, E.; Betsu, B.D.; Beyene, A.S.; Bhala, N.; Bhatt, S.; Biadgilign, S.; Bienhoff, K.; Bikbov, B.; Biryukov, S.; Bisanzio, D.; Bjertness, E.; Blore, J.; Borschmann, R.; Boufous, S.; Brainin, M.; Brazinova, A.; Breitborde, N.J.K.; Brown, J.; Buchbinder, R.; Buckle, G.C.; Butt, Z.A.; Calabria, B.; Campos-Nonato, I.R.; Campuzano, J.C.; Carabin, H.; Cárdenas, R.; Carpenter, D.O.; Carrero, J.J.; Castañeda-Orjuela, C.A.; Rivas, J.C.; Catalá-López, F.; Chang, J-C.; Chiang, P.P-C.; Chibueze, C.E.; Chisumpa, V.H.; Choi, J-Y.J.; Chowdhury, R.; Christensen, H.; Christopher, D.J.; Ciobanu, L.G.; Cirillo, M.; Coates, M.M.; Colquhoun, S.M.; Cooper, C.; Cortinovis, M.; Crump, J.A.; Damtew, S.A.; Dandona, R.; Daoud, F.; Dargan, P.I. das Neves, J.; Davey, G.; Davis, A.C.; Leo, D.D.; Degenhardt, L.; Gobbo, L.C.D.; Dellavalle, R.P.; Deribe, K.; Deribew, A.; Derrett, S.; Jarlais, D.C.D.; Dharmaratne, S.D.; Dhillon, P.K.; Diaz-Torné, C.; Ding, E.L.; Driscoll, T.R.; Duan, L.; Dubey, M.; Duncan, B.B.; Ebrahimi, H.; Ellenbogen, R.G.; Elyazar, I.; Endres, M.; Endries, A.Y.; Ermakov, S.P.; Eshrati, B.; Estep, K.; Farid, T.A.; Farinha, C.S.S.; Faro, A.; Farvid, M.S.; Farzadfar, F.; Feigin, V.L.; Felson, D.T.; Fereshtehnejad, S-M.; Fernandes, J.G.; Fernandes, J.C.; Fischer, F.; Fitchett, J.R.A.; Foreman, K.; Fowkes, F.G.R.; Fox, J.; Franklin, R.C.; Friedman, J.; Frostad, J.; Fürst, T.; Futran, N.D.; Gabbe, B.; Ganguly, P.; Gankpé, F.G.; Gebre, T.; Gebrehiwot, T.T.; Gebremedhin, A.T.; Geleijnse, J.M.; Gessner, B.D.; Gibney, K.B.; Ginawi, I.A.M.; Giref, A.Z.; Giroud, M.; Gishu, M.D.; Giussani, G.; Glaser, E.; Godwin, W.W.; Gomez-Dantes, H.; Gona, P.; Goodridge, A.; Gopalani, S.V.; Gotay, C.C.; Goto, A.; Gouda, H.N.; Grainger, R.; Greaves, F.; Guillemin, F.; Guo, Y.; Gupta, R.; Gupta, R.; Gupta, V.; Gutiérrez, R.A.; Haile, D.; Hailu, A.D.; Hailu, G.B.; Halasa, Y.A.; Hamadeh, R.R.; Hamidi, S.; Hammami, M.; Hancock, J.; Handal, A.J.; Hankey, G.J.; Hao, Y.; Harb, H.L.; Harikrishnan, S.; Haro, J.M.; Havmoeller, R.; Hay, R.J.; Heredia-Pi, I.B.; Heydarpour, P.; Hoek, H.W.; Horino, M.; Horita, N.; Hosgood, H.D.; Hoy, D.G.; Htet, A.S.; Huang, H.; Huang, J.J.; Huynh, C.; Iannarone, M.; Iburg, K.M.; Innos, K.; Inoue, M.; Iyer, V.J.; Jacobsen, K.H.; Jahanmehr, N.; Jakovljevic, M.B.; Javanbakht, M.; Jayaraman, S.P.; Jayatilleke, A.U.; Jee, S.H.; Jeemon, P.; Jensen, P.N.; Jiang, Y.; Jibat, T.; Jimenez-Corona, A.; Jin, Y.; Jonas, J.B.; Kabir, Z.; Kalkonde, Y.; Kamal, R.; Kan, H.; Karch, A.; Karema, C.K.; Karimkhani, C.; Kasaeian, A.; Kaul, A.; Kawakami, N.; Keiyoro, P.N.; Kemp, A.H.; Keren, A.; Kesavachandran, C.N.; Khader, Y.S.; Khan, A.R.; Khan, E.A.; Khang, Y-H.; Khera, S.; Khoja, T.A.M.; Khubchandani, J.; Kieling, C.; Kim, P.; Kim, C.; Kim, D.; Kim, Y.J.; Kissoon, N.; Knibbs, L.D.; Knudsen, A.K.; Kokubo, Y.; Kolte, D.; Kopec, J.A.; Kosen, S.; Kotsakis, G.A.; Koul, P.A.; Koyanagi, A.; Kravchenko, M.; Defo, B.K.; Bicer, B.K.; Kudom, A.A.; Kuipers, E.J.; Kumar, G.A.; Kutz, M.; Kwan, G.F.; Lal, A.; Lalloo, R.; Lallukka, T.; Lam, H.; Lam, J.O.; Langan, S.M.; Larsson, A.; Lavados, P.M.; Leasher, J.L.; Leigh, J.; Leung, R.; Levi, M.; Li, Y.; Li, Y.; Liang, J.; Liu, S.; Liu, Y.; Lloyd, B.K.; Lo, W.D.; Logroscino, G.; Looker, K.J.; Lotufo, P.A.; Lunevicius, R.; Lyons, R.A.; Mackay, M.T.; Magdy, M.; Razek, A.E.; Mahdavi, M.; Majdan, M.; Majeed, A.; Malekzadeh, R.; Marcenes, W.; Margolis, D.J.; Martinez-Raga, J.; Masiye, F.; Massano, J.; McGarvey, S.T.; McGrath, J.J.; McKee, M.; McMahon, B.J.; Meaney, P.A.; Mehari, A.; Mejia-Rodriguez, F.; Mekonnen, A.B.; Melaku, Y.A.; Memiah, P.; Memish, Z.A.; Mendoza, W.; Meretoja, A.; Meretoja, T.J.; Mhimbira, F.A.; Millear, A.; Miller, T.R.; Mills, E.J.; Mirarefin, M.; Mitchell, P.B.; Mock, C.N.; Mohammadi, A.; Mohammed, S.; Monasta, L.; Hernandez, J.C.M.; Montico, M.; Mooney, M.D.; Moradi-Lakeh, M.; Morawska, L.; Mueller, U.O.; Mullany, E.; Mumford, J.E.; Murdoch, M.E.; Nachega, J.B.; Nagel, G.; Naheed, A.; Naldi, L.; Nangia, V.; Newton, J.N.; Ng, M.; Ngalesoni, F.N.; Nguyen, Q.L.; Nisar, M.I.; Pete, P.M.N.; Nolla, J.M.; Norheim, O.F.; Norman, R.E.; Norrving, B.; Nunes, B.P.; Ogbo, F.A.; Oh, I-H.; Ohkubo, T.; Olivares, P.R.; Olusanya, B.O.; Olusanya, J.O.; Ortiz, A.; Osman, M.; Ota, E.; Pa, M.; Park, E-K.; Parsaeian, M.; de Azeredo Passos, V.M.; Caicedo, A.J.P.; Patten, S.B.; Patton, G.C.; Pereira, D.M.; Perez-Padilla, R.; Perico, N.; Pesudovs, K.; Petzold, M.; Phillips, M.R.; Piel, F.B.; Pillay, J.D.; Pishgar, F.; Plass, D.; Platts-Mills, J.A.; Polinder, S.; Pond, C.D.; Popova, S.; Poulton, R.G.; Pourmalek, F.; Prabhakaran, D.; Prasad, N.M.; Qorbani, M.; Rabiee, R.H.S.; Radfar, A.; Rafay, A.; Rahimi, K.; Rahimi-Movaghar, V.; Rahman, M.; Rahman, M.H.U.; Rahman, S.U.; Rai, R.K.; Rajsic, S.; Ram, U.; Rao, P.; Refaat, A.H.; Reitsma, M.B.; Remuzzi, G.; Resnikoff, S.; Reynolds, A.; Ribeiro, A.L.; Blancas, M.J.R.; Roba, H.S.; Rojas-Rueda, D.; Ronfani, L.; Roshandel, G.; Roth, G.A.; Rothenbacher, D.; Roy, A.; Sagar, R.; Sahathevan, R.; Sanabria, J.R.; Sanchez-Niño, M.D.; Santos, I.S.; Santos, J.V.; Sarmiento-Suarez, R.; Sartorius, B.; Satpathy, M.; Savic, M.; Sawhney, M.; Schaub, M.P.; Schmidt, M.I.; Schneider, I.J.C.; Schöttker, B.; Schwebel, D.C.; Scott, J.G.; Seedat, S.; Sepanlou, S.G.; Servan-Mori, E.E.; Shackelford, K.A.; Shaheen, A.; Shaikh, M.A.; Sharma, R.; Sharma, U.; Shen, J.; Shepard, D.S.; Sheth, K.N.; Shibuya, K.; Shin, M-J.; Shiri, R.; Shiue, I.; Shrime, M.G.; Sigfusdottir, I.D.; Silva, D.A.S.; Silveira, D.G.A.; Singh, A.; Singh, J.A.; Singh, O.P.; Singh, P.K.; Sivonda, A.; Skirbekk, V.; Skogen, J.C.; Sligar, A.; Sliwa, K.; Soljak, M.; Søreide, K.; Sorensen, R.J.D.; Soriano, J.B.; Sposato, L.A.; Sreeramareddy, C.T.; Stathopoulou, V.; Steel, N.; Stein, D.J.; Steiner, T.J.; Steinke, S.; Stovner, L.; Stroumpoulis, K.; Sunguya, B.F.; Sur, P.; Swaminathan, S.; Sykes, B.L.; Szoeke, C.E.I.; Tabarés-Seisdedos, R.; Takala, J.S.; Tandon, N.; Tanne, D.; Tavakkoli, M.; Taye, B.; Taylor, H.R.; Ao, B.J.T.; Tedla, B.A.; Terkawi, A.S.; Thomson, A.J.; Thorne-Lyman, A.L.; Thrift, A.G.; Thurston, G.D.; Tobe-Gai, R.; Tonelli, M.; Topor-Madry, R.; Topouzis, F.; Tran, B.X.; Truelsen, T.; Dimbuene, Z.T.; Tsilimbaris, M.; Tura, A.K.; Tuzcu, E.M.; Tyrovolas, S.; Ukwaja, K.N.; Undurraga, E.A.; Uneke, C.J.; Uthman, O.A.; van Gool, C.H.; Varakin, Y.Y.; Vasankari, T.; Venketasubramanian, N.; Verma, R.K.; Violante, F.S.; Vladimirov, S.K.; Vlassov, V.V.; Vollset, S.E.; Wagner, G.R.; Waller, S.G.; Wang, L.; Watkins, D.A.; Weichenthal, S.; Weiderpass, E.; Weintraub, R.G.; Werdecker, A.; Westerman, R.; White, R.A.; Williams, H.C.; Wiysonge, C.S.; Wolfe, C.D.A.; Won, S.; Woodbrook, R.; Wubshet, M.; Xavier, D.; Xu, G.; Yadav, A.K.; Yan, L.L.; Yano, Y.; Yaseri, M.; Ye, P.; Yebyo, H.G.; Yip, P.; Yonemoto, N.; Yoon, S-J.; Younis, M.Z.; Yu, C.; Zaidi, Z.; Zaki, M.E.S.; Zeeb, H.; Zhou, M.; Zodpey, S.; Zuhlke, L.J.; Murray, C.J.L. Global, regional, and national incidence, prevalence, and years lived with disability for 310 diseases and injuries, 1990–2015: A systematic analysis for the Global Burden of Disease Study 2015. Lancet, 2016, 388(10053), 1545-1602. doi: 10.1016/S0140-6736(16)31678-6 PMID: 27733282Glyn-Jones, S.; Palmer, A.J.R.; Agricola, R.; Price, A.J.; Vincent, T.L.; Weinans, H.; Carr, A.J. Osteoarthritis. Lancet, 2015, 386(9991), 376-387. doi: 10.1016/S0140-6736(14)60802-3 PMID: 25748615Goldring, M.B.; Marcu, K.B. Cartilage homeostasis in health and rheumatic diseases. Arthritis Res. Ther., 2009, 11(3), 224. doi: 10.1186/ar2592 PMID: 19519926Akkiraju, H.; Nohe, A. Role of chondrocytes in cartilage formation, progression of osteoarthritis and cartilage regeneration. J. Dev. Biol., 2015, 3(4), 177-192. doi: 10.3390/jdb3040177 PMID: 27347486Lepetsos, P.; Papavassiliou, A.G. ROS/oxidative stress signaling in osteoarthritis. Biochim. Biophys. Acta Mol. Basis Dis., 2016, 1862(4), 576-591. doi: 10.1016/j.bbadis.2016.01.003 PMID: 26769361Lambert, C.; Dubuc, J.E.; Montell, E.; Vergés, J.; Munaut, C.; Noël, A.; Henrotin, Y. Gene expression pattern of cells from inflamed and normal areas of osteoarthritis synovial membrane. Arthritis Rheumatol., 2014, 66(4), 960-968. doi: 10.1002/art.38315 PMID: 24757147Xiang, J.; Jiang, T.; Zhang, W.; Xie, W.; Tang, X.; Zhang, J. Human umbilical cord-derived mesenchymal stem cells enhanced HK-2 cell autophagy through MicroRNA-145 by inhibiting the PI3K/AKT/mTOR signaling pathway. Exp. Cell Res., 2019, 378(2), 198-205. doi: 10.1016/j.yexcr.2019.03.019 PMID: 30880031Wu, G.; Yu, W.; Zhang, M.; Yin, R.; Wu, Y.; Liu, Q. MicroRNA-145-3p suppresses proliferation and promotes apotosis and autophagy of osteosarcoma cell by targeting HDAC4. Artif. Cells Nanomed. Biotechnol., 2018, 46(Suppl. 2), 579-586. doi: 10.1080/21691401.2018.1464459 PMID: 29893594Ravanan, P.; Srikumar, I.F.; Talwar, P. Autophagy: The spotlight for cellular stress responses. Life Sci., 2017, 188, 53-67. doi: 10.1016/j.lfs.2017.08.029 PMID: 28866100D’Adamo, S.; Silvia, C.; Manuela, M.; Ylenia, S.; Rosa, M.R.; Flavio, F. MicroRNAs and autophagy: Fine players in the control of chondrocyte homeostatic activities in osteoarthritis. Oxid. Med. Cell. Longev., 2017, 2017, 3720128.Wang, X.Z.; Li, W.X. Changes of serum inflammatory factors and miR-145 expression in patients with osteoarthritis before and after treatment and their clinical value. World J. Clin. Cases, 2019, 7(19), 2963-2975. doi: 10.12998/wjcc.v7.i19.2963 PMID: 31624744Cutolo, M.; Berenbaum, F.; Hochberg, M.; Punzi, L.; Reginster, J.Y. Commentary on recent therapeutic guidelines for osteoarthritis. Semin. Arthritis Rheum., 2015, 44(6), 611-617. doi: 10.1016/j.semarthrit.2014.12.003 PMID: 25677861Hanna, J.; Hossain, G.S.; Kocerha, J. The potential for microRNA therapeutics and clinical research. Front. Genet., 2019, 10, 478. doi: 10.3389/fgene.2019.00478 PMID: 31156715Reid, G.; Kao, S.C.; Pavlakis, N.; Brahmbhatt, H.; MacDiarmid, J.; Clarke, S.; Boyer, M.; van Zandwijk, N. Clinical development of TargomiRs, a miRNA mimic-based treatment for patients with recurrent thoracic cancer. Epigenomics, 2016, 8(8), 1079-1085. doi: 10.2217/epi-2016-0035 PMID: 27185582Lanford, R.E.; Hildebrandt-Eriksen, E.S.; Petri, A.; Persson, R.; Lindow, M.; Munk, M.E.; Kauppinen, S.; Ørum, H. Therapeutic silencing of microRNA-122 in primates with chronic hepatitis C virus infection. Science, 2010, 327(5962), 198-201. doi: 10.1126/science.1178178 PMID: 19965718Singh, R.K.; Prasad, D.N.; Bhardwaj, T.R. Synthesis, physicochemical and kinetic studies of redox derivative of bis(2-chloroethylamine) as alkylating cytotoxic agent for brain delivery. Arab. J. Chem., 2015, 8(3), 380-387. doi: 10.1016/j.arabjc.2012.11.005Singh, R.K.; Prasad, D.N.; Bhardwaj, T.R. Synthesis in vitro/in vivo evaluation and in silico physicochemical study of prodrug approach for brain targeting of alkylating agent. Med. Chem. Res., 2013, 22(11), 5324-5336. doi: 10.1007/s00044-013-0537-0Higashi, K.; Yamada, Y.; Minatoguchi, S.; Baba, S.; Iwasa, M.; Kanamori, H.; Kawasaki, M.; Nishigaki, K.; Takemura, G.; Kumazaki, M.; Akao, Y.; Minatoguchi, S. MicroRNA-145 repairs infarcted myocardium by accelerating cardiomyocyte autophagy. Am. J. Physiol. Heart Circ. Physiol., 2015, 309(11), H1813-H1826. doi: 10.1152/ajpheart.00709.2014 PMID: 26432843Dhiman, A.; Sharma, R.; Singh, R.K. Target-based anticancer indole derivatives and insight into structure‒activity relationship: A mechanistic review update (2018–2021). Acta Pharm. Sin. B, 2022, 12(7), 3006-3027. doi: 10.1016/j.apsb.2022.03.021 PMID: 35865090Singh, R.K. Key Heterocyclic Cores for Smart Anticancer Drug–Design Part II; Bentham Science Publishers, 2022. doi: 10.2174/97898150400431220201Wang, J.; Sun, Z.; Yan, S.; Gao, F. Effect of miR 145 on gastric cancer cells. Mol. Med. Rep., 2019, 19(5), 3403-3410. doi: 10.3892/mmr.2019.10015 PMID: 30864704Lin, X.; Zhang, Y.; Liu, L.; McKeehan, W.L.; Shen, Y.; Song, S.; Wang, F. FRS2α is essential for the fibroblast growth factor to regulate the mTOR pathway and autophagy in mouse embryonic fibroblasts. Int. J. Biol. Sci., 2011, 7(8), 1114-1121. doi: 10.7150/ijbs.7.1114 PMID: 21927580Li, B.; Ding, C.M.; Li, Y.X.; Peng, J.C.; Geng, N.; Qin, W.W. MicroRNA 145 inhibits migration and induces apoptosis in human non small cell lung cancer cells through regulation of the EGFR/PI3K/AKT signaling pathway. Oncol. Rep., 2018, 40(5), 2944-2954. doi: 10.3892/or.2018.6666 PMID: 30226581