MicroRNA‑106b serves as a prognostic biomarker and is associated with cell proliferation, migration, and invasion in osteosarcoma

Xu,Ke; Xiong,Wenhua; Zhao,Shoujun; Wang,Bin

doi:10.3892/ol.2019.10666

MicroRNA‑106b serves as a prognostic biomarker and is associated with cell proliferation, migration, and invasion in osteosarcoma

Authors:
- Ke Xu
- Wenhua Xiong
- Shoujun Zhao
- Bin Wang
View Affiliations

Affiliations: Orthopedics Centre, Ningbo No. 2 Hospital, Ningbo, Zhejiang 315010, P.R. China
Published online on: July 25, 2019 https://doi.org/10.3892/ol.2019.10666
Pages: 3342-3348

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) have been demonstrated to be involved in tumor progression of various human malignancies. The purpose of this study was to investigate the expression patterns and prognostic value of microRNA‑106b (miR‑106b) in osteosarcoma (OS) and to examine its functional role in OS progression. Reverse transcription‑quantitative PCR (RT‑qPCR) was used to estimate the expression of miR‑106b in OS tissues and cells. The prognostic value of miR‑106b in OS was evaluated by plotting Kaplan‑Meier survival curves and performing Cox analyses. Cell experiments were carried out to examine the effects of miR‑106b on OS cell proliferation, migration, and invasion. The expression of miR‑106b was elevated in both OS tissues and cells compared with the expression in normal control tissues and cells (P<0.001). miR‑106b expression was associated with metastasis (P=0.028) and Tumor‑Node‑Metastasis stage (P=0.017). Patients with high miR‑106b expression levels had a poorer overall survival rate compared with those with low miR‑106b expression levels (log‑rank P=0.001). Multivariate Cox analyses indicated that miR‑106b expression was an independent prognostic factor for patients with OS (hazard ratio=2.769; 95% confidence interval=1.369‑5.599; P=0.005). The results of cell experiments implied that the upregulation of miR‑106b could promote OS cell proliferation, migration and invasion, whereas the downregulation of miR‑106b could suppress these functions (P<0.05). Taken together, this study's results indicated that the overexpression of miR‑106b is associated with a poor prognosis for patients with OS and that overexpression promotes OS cell proliferation, migration, and invasion. This study may provide a novel prognostic biomarker and a candidate therapeutic target for OS treatment.

View Figures

View References

1	Torre LA, Bray F, Siegel RL, Ferlay J, Lortet-Tieulent J and Jemal A: Global cancer statistics, 2012. CA Cancer J Clin. 65:87–108. 2015. View Article : Google Scholar : PubMed/NCBI
2	Ottaviani G and Jaffe N: The epidemiology of osteosarcoma. Cancer Treat Res. 152:3–13. 2009. View Article : Google Scholar : PubMed/NCBI
3	McTiernan A, Jinks RC, Sydes MR, Uscinska B, Hook JM, van Glabbeke M, Bramwell V, Lewis IJ, Taminiau AH, Nooij MA, et al: Presence of chemotherapy-induced toxicity predicts improved survival in patients with localised extremity osteosarcoma treated with doxorubicin and cisplatin: A report from the European Osteosarcoma Intergroup. Eur J Cancer. 48:703–712. 2012. View Article : Google Scholar : PubMed/NCBI
4	Siegel RL, Miller KD and Jemal A: Cancer statistics, 2017. CA Cancer J Clin. 67:7–30. 2017. View Article : Google Scholar : PubMed/NCBI
5	Li XP, Cao GW, Sun Q, Yang C, Yan B, Zhang MY, Fu YF and Yang LM: Cancer incidence and patient survival rates among the residents in the Pudong New Area of Shanghai between 2002 and 2006. Chin J Cancer. 32:512–519. 2013.PubMed/NCBI
6	Luetke A, Meyers PA, Lewis I and Juergens H: Osteosarcoma treatment-where do we stand? A state of the art review. Cancer Treat Rev. 40:523–532. 2014. View Article : Google Scholar : PubMed/NCBI
7	Feng Y, Dong YW, Song YN, Xiao JH, Guo XY, Jiang WL and Lu LG: MicroRNA-449a is a potential predictor of colitis-associated colorectal cancer progression. Oncol Rep. 40:1684–1694. 2018.PubMed/NCBI
8	Peng X, Zha L, Chen A and Wang Z: HOXA5 is a tumor suppressor gene that is decreased in gastric cancer. Oncol Rep. 40:1317–1329. 2018.PubMed/NCBI
9	Zhou B, Li Z, Yang H and He N: Extracellular miRNAs: Origin, function and biomarkers in hepatic diseases. J Biomed Nanotechnol. 10:2865–2890. 2014. View Article : Google Scholar : PubMed/NCBI
10	Chen Z, Tang ZY, He Y, Liu LF, Li DJ and Chen X: miRNA-205 is a candidate tumor suppressor that targets ZEB2 in renal cell carcinoma. Oncol Res Treat. 37:658–664. 2014. View Article : Google Scholar : PubMed/NCBI
11	Zhao J, Xu J and Zhang R: MicroRNA-539 inhibits colorectal cancer progression by directly targeting SOX4. Oncol Lett. 16:2693–2700. 2018.PubMed/NCBI
12	Chen K, Chen Y, Chen Z, Shi Y, He Z, Ding B, Wang C and Yu L: miR-134 increases the antitumor effects of cytarabine by targeting Mnks in acute myeloid leukemia cells. Onco Targets Ther. 11:3141–3147. 2018. View Article : Google Scholar : PubMed/NCBI
13	Liu Y, Li L, Liu Z, Yuan Q and Lu X: Downregulation of MiR-431 expression associated with lymph node metastasis and promotes cell invasion in papillary thyroid carcinoma. Cancer Biomark. 22:727–732. 2018. View Article : Google Scholar : PubMed/NCBI
14	Liu H, Cao B, Zhao Y, Liang H and Hao F: Upregulated miR-221/222 promotes cell proliferation and invasion and is associated with invasive features in retinoblastoma. Cancer Biomark. 22:621–629. 2018. View Article : Google Scholar : PubMed/NCBI
15	Liu N, Yang H and Wang H: miR-598 acts as a tumor suppressor in human gastric cancer by targeting IGF-1R. Onco Targets Ther. 11:2911–2923. 2018. View Article : Google Scholar : PubMed/NCBI
16	Liu W, Wan X, Mu Z, Li F, Wang L, Zhao J and Huang X: MiR-1256 suppresses proliferation and migration of non-small cell lung cancer via regulating TCTN1. Oncol Lett. 16:1708–1714. 2018.PubMed/NCBI
17	Arabi L, Gsponer JR, Smida J, Nathrath M, Perrina V, Jundt G, Ruiz C, Quagliata L and Baumhoer D: Upregulation of the miR-17-92 cluster and its two paraloga in osteosarcoma-reasons and consequences. Genes Cancer. 5:56–63. 2014.PubMed/NCBI
18	Edge SB, Byrd DR, Compton CC, Fritz AG, Greene FL and Trotti A: AJCC cancer staging manual. 7th. New York: Springer; 2010
19	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
20	Xiang J, Wu Y, Li DS, Wang ZY, Shen Q, Sun TQ, Guan Q and Wang YJ: miR-584 suppresses invasion and cell migration of thyroid carcinoma by regulating the target oncogene ROCK1. Oncol Res Treat. 38:436–440. 2015. View Article : Google Scholar : PubMed/NCBI
21	Li L and Li S: miR-205-5p inhibits cell migration and invasion in prostatic carcinoma by targeting ZEB1. Oncol Lett. 16:1715–1721. 2018.PubMed/NCBI
22	Deng Y and Chen Y: Increased expression of miR-29a and its prognostic significance in patients with cholangiocarcinoma. Oncol Res Treat. 40:128–132. 2017. View Article : Google Scholar : PubMed/NCBI
23	Dan B, Luo J, Li K and Chen S: Prognostic value of miR-375 for survival outcomes in various cancers: A systematic review and meta-analysis. Oncol Res Treat. 41:47–50. 2018. View Article : Google Scholar : PubMed/NCBI
24	Zhou W, Hao M, Du X, Chen K, Wang G and Yang J: Advances in targeted therapy for osteosarcoma. Discov Med. 17:301–307. 2014.PubMed/NCBI
25	Zhang J, Wang D, Xiong J, Chen L and Huang J: MicroRNA-33a-5p suppresses growth of osteosarcoma cells and is downregulated in human osteosarcoma. Oncol Lett. 10:2135–2141. 2015. View Article : Google Scholar : PubMed/NCBI
26	Zhang H, Wang Y, Xu T, Li C, Wu J, He Q, Wang G, Ding C, Liu K, Tang H and Ji F: Increased expression of microRNA-148a in osteosarcoma promotes cancer cell growth by targeting PTEN. Oncol Lett. 12:3208–3214. 2016. View Article : Google Scholar : PubMed/NCBI
27	Mao JH, Zhou RP, Peng AF, Liu ZL, Huang SH, Long XH and Shu Y: microRNA-195 suppresses osteosarcoma cell invasion and migration in vitro by targeting FASN. Oncol Lett. 4:1125–1129. 2012. View Article : Google Scholar : PubMed/NCBI
28	Li S, Gao Y, Wang Y, Wang K, Dai ZP, Xu D, Liu W, Li ZL, Zhang ZD, Yang SH and Yang C: Serum microRNA-17 functions as a prognostic biomarker in osteosarcoma. Oncol Lett. 12:4905–4910. 2016. View Article : Google Scholar : PubMed/NCBI
29	Tan W, Li Y, Lim SG and Tan TM: miR-106b-25/miR-17-92 clusters: Polycistrons with oncogenic roles in hepatocellular carcinoma. World J Gastroenterol. 20:5962–5972. 2014. View Article : Google Scholar : PubMed/NCBI
30	Verboon LJ, Obulkasim A, de Rooij JD, Katsman-Kuipers JE, Sonneveld E, Baruchel A, Trka J, Reinhardt D, Pieters R, Cloos J, et al: MicroRNA-106b~25 cluster is upregulated in relapsed MLL-rearranged pediatric acute myeloid leukemia. Oncotarget. 7:48412–48422. 2016. View Article : Google Scholar : PubMed/NCBI
31	Ni X, Xia T, Zhao Y, Zhou W, Wu N, Liu X, Ding Q, Zha X, Sha J and Wang S: Downregulation of miR-106b induced breast cancer cell invasion and motility in association with overexpression of matrix metalloproteinase 2. Cancer Sci. 105:18–25. 2014. View Article : Google Scholar : PubMed/NCBI
32	Yen CS, Su ZR, Lee YP, Liu IT and Yen CJ: miR-106b promotes cancer progression in hepatitis B virus-associated hepatocellular carcinoma. World J Gastroenterol. 22:5183–5192. 2016. View Article : Google Scholar : PubMed/NCBI
33	Xu M, Zhang YY, Wang HF and Yang GS: The expression and function of miRNA-106 in pediatric osteosarcoma. Eur Rev Med Pharmacol Sci. 21:715–722. 2017.PubMed/NCBI
34	Li KK, Xia T, Ma FM, Zhang R, Mao Y, Wang Y, Zhou L, Lau KM and Ng HK: miR-106b is overexpressed in medulloblastomas and interacts directly with PTEN. Neuropathol Appl Neurobiol. 41:145–164. 2015. View Article : Google Scholar : PubMed/NCBI
35	Dai F, Liu T, Zheng S, Liu Q, Yang C, Zhou J, Chen Y, Sheyhidin I and Lu X: MiR-106b promotes migration and invasion through enhancing EMT via downregulation of Smad 7 in Kazakh's esophageal squamous cell carcinoma. Tumour Biol. 37:14595–14604. 2016. View Article : Google Scholar : PubMed/NCBI