miR-141-3p suppresses proliferation and promotes apoptosis by targeting GLI2 in osteosarcoma cells Retraction in /10.3892/or.2023.8576

Wang,Nan; Li,Pengcheng; Liu,Wei; Wang,Ningning; Lu,Zhi; Feng,Jianzhou; Zeng,Xiandong; Yang,Jiujie; Wang,Yong; Zhao,Wei

doi:10.3892/or.2017.6150

miR-141-3p suppresses proliferation and promotes apoptosis by targeting GLI2 in osteosarcoma cells

Retraction in: /10.3892/or.2023.8576

Authors:
- Nan Wang
- Pengcheng Li
- Wei Liu
- Ningning Wang
- Zhi Lu
- Jianzhou Feng
- Xiandong Zeng
- Jiujie Yang
- Yong Wang
- Wei Zhao
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Affiliations: The 4th Department of Orthopedic Surgery, Central Hospital Affiliated to Shenyang Medical College, Shenyang, Liaoning 110024, P.R. China, Department of Minimal Invasive Spinal Surgery, The First Hospital of Jilin University, Changchun, Jilin 130021, P.R. China, The 2nd Department of Cardiology, Central Hospital Affiliated to Shenyang Medical College, Shenyang, Liaoning 110024, P.R. China, Department of Nuclear Medicine, The 1st Affiliated Hospital of Dalian Medical University, Dalian, Liaoning 116011, P.R. China, Department of Surgical Oncology, Central Hospital Affiliated to Shenyang Medical College, Shenyang, Liaoning 110024, P.R. China
Published online on: December 12, 2017 https://doi.org/10.3892/or.2017.6150
Pages: 747-754

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Abstract

MicroRNAs (miRNAs) have been reported as key regulators in numerous diseases including osteosarcoma. The function of microRNA-141-3p (miR-141-3p) and whether this function is achieved by regulation of GLI family zinc finger 2 (GLI2) in osteosarcoma remain unclear. In the present study, we found decreased expression of miR-141-3p, but increased expression of GLI2 in osteosarcoma tissues and cell lines. In addition, we demonstrated a negative correlation between miR-141-3p and GLI2. Furthermore, we revealed that elevation of miR-141-3p resulted in a marked inhibition of proliferation and promotion of apoptosis as well as an obviously decrease in GLI2 in osteosarcoma cell lines. Furthermore, we determined that GLI2 is a target of miR-141-3p by a constructed luciferase assay. In addition, we showed that miR-141-3p could negatively regulate GLI2 and its downstream parathyroid hormone-related protein 1 (PTHRP1). Finally, through a series of antisense experiments we confirmed that the effect of miR-141-3p on proliferation and apoptosis was achieved through the GLI2 pathway in osteosarcoma cells. The findings of the present study may provide a new target for treating osteosarcoma.

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1	Messerschmitt PJ, Garcia RM, Abdul-Karim FW, Greenfield EM and Getty PJ: Osteosarcoma. J Am Acad Orthop Surg. 17:515–527. 2009. View Article : Google Scholar : PubMed/NCBI
2	Mirabello L, Troisi RJ and Savage SA: International osteosarcoma incidence patterns in children and adolescents, middle ages and elderly persons. Int J Cancer. 125:229–234. 2009. View Article : Google Scholar : PubMed/NCBI
3	Anderson ME: Update on survival in osteosarcoma. Orthop Clin North Am. 47:283–292. 2016. View Article : Google Scholar : PubMed/NCBI
4	Vijayakumar V, Lowery R, Zhang X, Hicks C, Rezeanu L, Barr J, Giles H, Vijayakumar S and Megason G: Pediatric osteosarcoma: A single institution's experience. South Med J. 107:671–675. 2014. View Article : Google Scholar : PubMed/NCBI
5	Nagao-Kitamoto H, Nagata M, Nagano S, Kitamoto S, Ishidou Y, Yamamoto T, Nakamura S, Tsuru A, Abematsu M, Fujimoto Y, et al: GLI2 is a novel therapeutic target for metastasis of osteosarcoma. Int J Cancer. 136:1276–1284. 2015. View Article : Google Scholar : PubMed/NCBI
6	Nagao-Kitamoto H, Setoguchi T, Kitamoto S, Nakamura S, Tsuru A, Nagata M, Nagano S, Ishidou Y, Yokouchi M, Kitajima S, et al: Ribosomal protein S3 regulates GLI2-mediated osteosarcoma invasion. Cancer Lett. 356:855–861. 2015. View Article : Google Scholar : PubMed/NCBI
7	Yang W, Liu X, Choy E, Mankin H, Hornicek FJ and Duan Z: Targeting hedgehog-GLI-2 pathway in osteosarcoma. J Orthop Res. 31:502–509. 2013. View Article : Google Scholar : PubMed/NCBI
8	Nakamura S, Nagano S, Nagao H, Ishidou Y, Yokouchi M, Abematsu M, Yamamoto T, Komiya S and Setoguchi T: Arsenic trioxide prevents osteosarcoma growth by inhibition of GLI transcription via DNA damage accumulation. PloS One. 8:e694662013. View Article : Google Scholar : PubMed/NCBI
9	Nagao H, Ijiri K, Hirotsu M, Ishidou Y, Yamamoto T, Nagano S, Takizawa T, Nakashima K, Komiya S and Setoguchi T: Role of GLI2 in the growth of human osteosarcoma. J Pathol. 224:169–179. 2011. View Article : Google Scholar : PubMed/NCBI
10	Jin YY, Chen QJ, Xu K, Ren HT, Bao X, Ma YN, Wei Y and Ma HB: Involvement of microRNA-141-3p in 5-fluorouracil and oxaliplatin chemo-resistance in esophageal cancer cells via regulation of PTEN. Mol Cell Biochem. 422:161–170. 2016. View Article : Google Scholar : PubMed/NCBI
11	Lei K, Liang X, Gao Y, Xu B, Xu Y, Li Y, Tao Y, Shi W and Liu J: Lnc-ATB contributes to gastric cancer growth through a MiR-141-3p/TGFβ2 feedback loop. Biochem Biophys Res Commun. 484:514–521. 2017. View Article : Google Scholar : PubMed/NCBI
12	Li JZ, Li J, Wang HQ, Li X, Wen B and Wang YJ: MiR-141-3p promotes prostate cancer cell proliferation through inhibiting Krüppel-like factor-9 expression. Biochem Biophys Res Commun. 482:1381–1386. 2017. View Article : Google Scholar : PubMed/NCBI
13	Liep J, Kilic E, Meyer HA, Busch J, Jung K and Rabien A: Cooperative effect of miR-141-3p and miR-145-5p in the regulation of targets in clear cell renal cell carcinoma. PloS One. 11:e01578012016. View Article : Google Scholar : PubMed/NCBI
14	Liu CZ, Ye ZH, Ma J, He RQ, Liang HW, Peng ZG and Chen G: A qRT-PCR and gene functional enrichment study focused on downregulation of miR-141-3p in hepatocellular carcinoma and its clinicopathological significance. Technol Cancer Res Treat 1533034617705056. 2017.(Epub ahead of print). doi: 10.1177/1533034617705056.
15	Qiu W and Kassem M: miR-141-3p inhibits human stromal (mesenchymal) stem cell proliferation and differentiation. Biochim Biophys Acta. 1843:2114–2121. 2014. View Article : Google Scholar : PubMed/NCBI
16	Wang Y, Wang N, Zeng X, Sun J, Wang G, Xu H and Zhao W: MicroRNA-335 and its target Rock1 synergistically influence tumor progression and prognosis in osteosarcoma. Oncol Lett. 13:3057–3065. 2017.PubMed/NCBI
17	Wang Y, Sun J, Wei X, Luan L, Zeng X, Wang C and Zhao W: Decrease of miR-622 expression suppresses migration and invasion by targeting regulation of DYRK2 in colorectal cancer cells. OncoTargets Ther. 10:1091–1100. 2017. View Article : Google Scholar
18	Kyrylkova K, Kyryachenko S, Leid M and Kioussi C: Detection of apoptosis by TUNEL assay. Methods Mol Biol. 887:41–47. 2012. View Article : Google Scholar : PubMed/NCBI
19	Javelaud D, Pierrat MJ and Mauviel A: Crosstalk between TGF-β and hedgehog signaling in cancer. FEBS Lett. 586:2016–2025. 2012. View Article : Google Scholar : PubMed/NCBI
20	Mill P, Mo R, Fu H, Grachtchouk M, Kim PC, Dlugosz AA and Hui CC: Sonic hedgehog-dependent activation of Gli2 is essential for embryonic hair follicle development. Genes Dev. 17:282–294. 2003. View Article : Google Scholar : PubMed/NCBI
21	Javelaud D, Alexaki VI, Dennler S, Mohammad KS, Guise TA and Mauviel A: TGF-β/SMAD/GLI2 signaling axis in cancer progression and metastasis. Cancer Res. 71:5606–5610. 2011. View Article : Google Scholar : PubMed/NCBI
22	Lauth M and Toftgard R: Non-canonical activation of GLI transcription factors: Implications for targeted anti-cancer therapy. Cell Cycle. 6:2458–2463. 2007. View Article : Google Scholar : PubMed/NCBI
23	Boras-Granic K and Wysolmerski JJ: PTHrP and breast cancer: More than hypercalcemia and bone metastases. Breast Cancer Res. 14:3072012. View Article : Google Scholar : PubMed/NCBI
24	Hsu YL, Tsai EM, Hou MF, Wang TN, Hung JY and Kuo PL: Obtusifolin suppresses phthalate esters-induced breast cancer bone metastasis by targeting parathyroid hormone-related protein. J Agric Food Chem. 62:11933–11940. 2014. View Article : Google Scholar : PubMed/NCBI
25	Huang DC, Yang XF, Ochietti B, Fadhil I, Camirand A and Kremer R: Parathyroid hormone-related protein: Potential therapeutic target for melanoma invasion and metastasis. Endocrinology. 155:3739–3749. 2014. View Article : Google Scholar : PubMed/NCBI
26	Nagamine K, Kitamura T, Yanagawa-Matsuda A, Ohiro Y, Tei K, Hida K, Higashino F, Totsuka Y and Shindoh M: Expression of parathyroid hormone-related protein confers malignant potential to mucoepidermoid carcinoma. Oncol Rep. 29:2114–2118. 2013. View Article : Google Scholar : PubMed/NCBI
27	Ongkeko WM, Burton D, Kiang A, Abhold E, Kuo SZ, Rahimy E, Yang M, Hoffman RM, Wang-Rodriguez J and Deftos LJ: Parathyroid hormone related-protein promotes epithelial-to-mesenchymal transition in prostate cancer. PloS One. 9:e858032014. View Article : Google Scholar : PubMed/NCBI
28	Walkley CR, Walia MK, Ho PW and Martin TJ: PTHrP, its receptor, and protein kinase A activation in osteosarcoma. Mol Cell Oncol. 1:e9656242014. View Article : Google Scholar : PubMed/NCBI
29	Ho PW, Goradia A, Russell MR, Chalk AM, Milley KM, Baker EK, Danks JA, Slavin JL, Walia M, Crimeen-Irwin B, et al: Knockdown of PTHR1 in osteosarcoma cells decreases invasion and growth and increases tumor differentiation in vivo. Oncogene. 34:2922–2933. 2015. View Article : Google Scholar : PubMed/NCBI
30	Verrando P, Capovilla M and Rahmani R: Trans-nonachlor decreases miR-141-3p levels in human melanocytes in vitro promoting melanoma cell characteristics and shows a multigenerational impact on miR-8 levels in Drosophila. Toxicology 368–369. 1–141. 2016.
31	Jiang Q, Wang Y and Shi X: Propofol inhibits neurogenesis of rat neural stem cells by upregulating MicroRNA-141-3p. Stem Cells Dev. 26:189–196. 2017. View Article : Google Scholar : PubMed/NCBI
32	Liu W, Wang X, Liu Z, Wang Y, Yin B, Yu P, Duan X, Liao Z, Chen Y, Liu C, et al: SGK1 inhibition induces autophagy-dependent apoptosis via the mTOR-Foxo3a pathway. Br J Cancer. 117:1139–1153. 2017. View Article : Google Scholar : PubMed/NCBI
33	Wang X, Lin B, Nie L and Li P: microRNA-20b contributes to high glucose-induced podocyte apoptosis by targeting SIRT7. Mol Med Rep. 16:5667–5674. 2017.PubMed/NCBI
34	Zhao J, Ou SL, Wang WY, Yan C and Chi LX: MicroRNA-1907 enhances atherosclerosis-associated endothelial cell apoptosis by suppressing Bcl-2. Am J Transl Res. 9:3433–3442. 2017.PubMed/NCBI
35	Acunzo M, Romano G, Wernicke D and Croce CM: MicroRNA and cancer-a brief overview. Adv Biol Regul. 57:1–9. 2015. View Article : Google Scholar : PubMed/NCBI
36	Geaghan M and Cairns MJ: MicroRNA and posttranscriptional dysregulation in psychiatry. Biol Psychiatry. 78:231–239. 2015. View Article : Google Scholar : PubMed/NCBI
37	Liu B, Li J and Cairns MJ: Identifying miRNAs, targets and functions. Brief Bioinform. 15:1–19. 2014. View Article : Google Scholar : PubMed/NCBI
38	Wang Y, Yang T, Zhang Z, Lu M, Zhao W, Zeng X and Zhang W: Long non-coding RNA TUG1 promotes migration and invasion by acting as a ceRNA of miR-335-5p in osteosarcoma cells. Cancer Sci. 108:859–867. 2017. View Article : Google Scholar : PubMed/NCBI
39	Wang Y, Zhao W and Fu Q: miR-335 suppresses migration and invasion by targeting ROCK1 in osteosarcoma cells. Mol Cell Biochem. 384:105–111. 2013. View Article : Google Scholar : PubMed/NCBI