MicroRNA-744 promotes proliferation of osteosarcoma cells by targeting PTEN

Yu,Wei; Chen,Peng-Bo; Chen,Fan-Cheng; Ding,Sheng-Long; Pan,Xiao-Yun

doi:10.3892/mmr.2020.11030

MicroRNA-744 promotes proliferation of osteosarcoma cells by targeting PTEN

Authors:
- Wei Yu
- Peng-Bo Chen
- Fan-Cheng Chen
- Sheng-Long Ding
- Xiao-Yun Pan
View Affiliations

Affiliations: Department of Orthopedic Surgery, The Second Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, P.R. China, Department of Orthopedic Surgery, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200092, P.R. China, Department of Orthopedic Surgery, Zhongshan Hospital, Fudan University, Shanghai 200433, P.R. China, Department of Orthopedics, Qingpu Branch of Zhongshan Hospital, Fudan University, Shanghai 201700, P.R. China
Published online on: March 18, 2020 https://doi.org/10.3892/mmr.2020.11030
Pages: 2276-2282

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

MicroRNAs (miRNAs/miRs) are non-coding RNAs that regulate protein synthesis by targeting mRNAs for translational repression or degradation. Previous studies have reported that aberrant expression of miR‑744 may be involved in human osteosarcoma; however, the underlying mechanisms remain elusive. In the present study, the expression levels of miR‑744 and its downstream signals were determined by reverse transcription‑quantitative PCR and western blotting. Cell proliferation was assessed using the bromodeoxyuridine assay, and the target of miR‑744 was investigated using a dual‑luciferase activity assay. The present study identified a significant upregulation of miR‑744 in osteosarcoma tissues compared with adjacent non‑tumor tissues. Furthermore, it was demonstrated that ectopic overexpression of miR‑744 induced by a miR‑744 precursor significantly enhanced proliferation of the osteosarcoma cell line MG63, whereas opposite results were observed following suppression of miR‑744 with its inhibitor. Moreover, as a unique anti‑oncogene, PTEN was identified as a direct target of miR‑744. It was confirmed that miR‑744 downregulated PTEN expression in MG63 cells by targeting the PTEN 3'untranslated region, and that the downstream AKT signal was also regulated by miR‑744. Collectively, the present results suggested that miR‑744 promoted proliferation of human osteosarcoma cells by directly regulating the PTEN/AKT signaling pathway.

View Figures

View References

1	Ameres SL and Zamore PD: Diversifying microRNA sequence and function. Nat Rev Mol Cell Biol. 14:475–488. 2013. View Article : Google Scholar : PubMed/NCBI
2	Ambros V: The functions of animal microRNAs. Nature. 431:350–355. 2004. View Article : Google Scholar : PubMed/NCBI
3	Esquela-Kerscher A and Slack FJ: Oncomirs-microRNAs with a role in cancer. Nat Rev Cancer. 6:259–269. 2006. View Article : Google Scholar : PubMed/NCBI
4	Calin GA and Croce CM: MicroRNA signatures in human cancers. Nat Rev Cancer. 6:857–866. 2006. View Article : Google Scholar : PubMed/NCBI
5	Saraf AJ, Fenger JM and Roberts RD: Osteosarcoma: Accelerating progress makes for a hopeful future. Front Oncol. 8:42018. View Article : Google Scholar : PubMed/NCBI
6	Xu J, Wang H, Hu Y, Zhang YS, Wen L, Yin F, Wang Z, Zhang Y, Li S, Miao Y, et al: Inhibition of CaMKIIα activity enhances antitumor effect of fullerene C60 nanocrystals by suppression of autophagic degradation. Adv Sci (Weinh). 6:1801233. 2019. View Article : Google Scholar : PubMed/NCBI
7	Liu JL, Li J, Xu JJ, Xiao F, Cui PL, Qiao ZG, Chen XD, Tao WD and Zhang XL: miR-144 inhibits tumor growth and metastasis in osteosarcoma via dual-suppressing RhoA/ROCK1 signaling pathway. Mol Pharmacol. 95:451–461. 2019. View Article : Google Scholar : PubMed/NCBI
8	Jianwei Z, Fan L, Xiancheng L, Enzhong B, Shuai L and Can L: MicroRNA 181a improves proliferation and invasion, suppresses apoptosis of osteosarcoma cell. Tumour Biol. 34:3331–3337. 2013. View Article : Google Scholar : PubMed/NCBI
9	Chen Z, Zhao G, Zhang Y, Ma Y, Ding Y and Xu N: miR-199b-5p promotes malignant progression of osteosarcoma by regulating HER2. J BUON. 23:1816–1824. 2018.PubMed/NCBI
10	Zhu KP, Zhang CL, Ma XL, Hu JP, Cai T and Zhang L: Analyzing the interactions of mRNAs and ncRNAs to predict competing endogenous RNA networks in osteosarcoma chemo-resistance. Mol Ther. 27:518–530. 2019. View Article : Google Scholar : PubMed/NCBI
11	Sun L, Liu M, Luan S, Shi Y and Wang Q: MicroRNA-744 promotes carcinogenesis in osteosarcoma through targeting LATS2. Oncol Lett. 18:2523–2529. 2019.PubMed/NCBI
12	Li JZ, Gao W, Lei WB, Zhao J, Chan JY, Wei WI, Ho WK and Wong TS: MicroRNA 744-3p promotes MMP-9-mediated metastasis by simultaneously suppressing PDCD4 and PTEN in laryngeal squamous cell carcinoma. Oncotarget. 7:58218–58233. 2016.PubMed/NCBI
13	Tamura M, Gu J, Matsumoto K, Aota S, Parsons R and Yamada KM: Inhibition of cell migration, spreading, and focal adhesions by tumor suppressor PTEN. Science. 280:1614–1617. 1998. View Article : Google Scholar : PubMed/NCBI
14	Rosenberg AE, Cleton-Jansen AM, de Pineux G, Deyrup AT, Hauben E and Squire J: Conventional osteosarcoma. WHO Classification of Tumours of Soft Tissue and Bone. 4th. Fletcher CDM, Bridge JA, Hogendoorn CWH and Mertens F: IARC Press; Lyon: pp. 282–288. 2013
15	Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods. 25:402–408. 2001. View Article : Google Scholar : PubMed/NCBI
16	Cantley LC and Neel BG: New insights into tumor suppression: PTEN suppresses tumor formation by restraining the phosphoinositide 3-kinase/AKT pathway. Proc Natl Acad Sci USA. 96:4240–4245. 1999. View Article : Google Scholar : PubMed/NCBI
17	Sansal I and Sellers WR: The biology and clinical relevance of the PTEN tumor suppressor pathway. J Clin Oncol. 22:2954–2963. 2004. View Article : Google Scholar : PubMed/NCBI
18	Yang H, Kong W, He L, Zhao JJ, O'Donnell JD, Wang J, Wenham RM, Coppola D, Kruk PA, Nicosia SV and Cheng JQ: MicroRNA expression profiling in human ovarian cancer: miR-214 induces cell survival and cisplatin resistance by targeting PTEN. Cancer Res. 68:425–433. 2008. View Article : Google Scholar : PubMed/NCBI
19	Zhang Y, Wang F, Li M, Yu Z, Qi R, Ding J, Zhang Z and Chen X: Self-Stabilized hyaluronate nanogel for intracellular codelivery of doxorubicin and cisplatin to osteosarcoma. Adv Sci (Weinh). 5:17008212018. View Article : Google Scholar : PubMed/NCBI
20	Li S, Zhang T, Xu W, Ding J, Yin F, Xu J, Sun W, Wang H, Sun M, Cai Z and Hua Y: Sarcoma-targeting peptide-decorated polypeptide nanogel intracellularly delivers shikonin for upregulated osteosarcoma necroptosis and diminished pulmonary metastasis. Theranostics. 8:1361–1375. 2018. View Article : Google Scholar : PubMed/NCBI
21	Zhou W, Li Y, Gou S, Xiong J, Wu H, Wang C, Yan H and Liu T: miR-744 increases tumorigenicity of pancreatic cancer by activating Wnt/β-catenin pathway. Oncotarget. 6:37557–37569. 2015. View Article : Google Scholar : PubMed/NCBI
22	Zhang M and Li H, Zhang Y and Li H: Oncogenic miR-744 promotes prostate cancer growth through direct targeting of LKB1. Oncol Lett. 17:2257–2265. 2019.PubMed/NCBI
23	Yu Q, Zhang F, Du Z and Xiang Y: Up-regulation of serum miR-744 predicts poor prognosis in patients with nasopharyngeal carcinoma. Int J Clin Exp Med. 8:13296–13302. 2015.PubMed/NCBI
24	Deng Y, Li Y, Fang Q, Luo H and Zhu G: microRNA-744 is downregulated in glioblastoma and inhibits the aggressive behaviors by directly targeting NOB1. Am J Cancer Res. 8:2238–2253. 2018.PubMed/NCBI
25	Xu AJ, Fu LN, Wu HX, Yao XL and Meng R: MicroRNA744 inhibits tumor cell proliferation and invasion of gastric cancer via targeting brainderived neurotrophic factor. Mol Med Rep. 16:5055–5061. 2017. View Article : Google Scholar : PubMed/NCBI
26	Shen J and Li M: MicroRNA-744 inhibits cellular proliferation and invasion of colorectal cancer by directly targeting oncogene Notch1. Oncol Res. Feb 22–2018.(Epub ahead of print). View Article : Google Scholar
27	Tan YL, Bai ZG, Zou WL, Ma XM, Wang TT, Guo W, Liu J, Li JS, Jie-Yin, Zang YJ and Zhang ZT: miR-744 is a potential prognostic marker in patients with hepatocellular carcinoma. Clin Res Hepatol Gastroenterol. 39:359–365. 2015. View Article : Google Scholar : PubMed/NCBI
28	Osaki M, Oshimura M and Ito H: PI3K-Akt pathway: Its functions and alterations in human cancer. Apoptosis. 9:667–676. 2004. View Article : Google Scholar : PubMed/NCBI
29	Colakoglu T, Yildirim S, Kayaselcuk F, Nursal TZ, Ezer A, Noyan T, Karakayali H and Haberal M: Clinicopathological significance of PTEN loss and the phosphoinositide 3-kinase/Akt pathway in sporadic colorectal neoplasms: Is PTEN loss predictor of local recurrence? Am J Surg. 195:719–725. 2008. View Article : Google Scholar : PubMed/NCBI
30	Saal LH, Holm K, Maurer M, Memeo L, Su T, Wang X, Yu JS, Malmström PO, Mansukhani M, Enoksson J, et al: PIK3CA mutations correlate with hormone receptors, node metastasis, and ERBB2, and are mutually exclusive with PTEN loss in human breast carcinoma. Cancer Res. 65:2554–2559. 2005. View Article : Google Scholar : PubMed/NCBI
31	Tang JM, He QY, Guo RX and Chang XJ: Phosphorylated Akt overexpression and loss of PTEN expression in non-small cell lung cancer confers poor prognosis. Lung Cancer. 51:181–191. 2006. View Article : Google Scholar : PubMed/NCBI