LncRNA DLX6-AS1 regulates osteosarcoma progression via the miR-200a-3p/GPM6P axis

  • Tianyi Wu Department of Orthopaedic Surgery, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai, China
  • Chen Huang Department of General Practice, XingRen Community Health Service Centre, Xuecheng Zone, ZaoZhuang, Shandong, China
  • Feng Wang Department of Orthopaedic Surgery, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai, China
Keywords: LncRNA DLX6-AS1, osteosarcoma, miR-200a-3p, GPM6B


LncRNA DLX6-AS1 takes part in the progression of various cancers. However, it is not elaborated clearly in osteosarcoma (OS) development. Therefore, we aimed to explore the impacts and specific mechanisms of DLX6-AS1 on the progression of OS. We estimated the pattern of DLX6-AS1 expression in Ost tissues and cells via quantitative reverse transcription polymerase chain reaction. A number of biochemical assays were carried out to assess the effects of DLX6-AS1. Target genes were predicted by bioinformatics methods. Then we used the transfection of si-RNA, miRNA inhibitor, and miRNA mimics to explore the underlying mechanisms and built tumor xenograft models for the in vivo experiments. A higher expression of DLX6-AS1 was found in OS tissues and cell lines, while knockdown of DXL6-AS1 suppressed OS cell metastasis and proliferation in vitro and in vivo. Mechanistically, it was revealed that DXL6-AS1 sponged miR-200a-3p, thus positively regulating the downstream GPM6B. In summary, DLX6-AS1 knockdown would inhibit OS cell migration, cell invasion, and cell proliferation, in which the DXL6-AS1/ miR-200a-3p/ GPM6B axis played a critical role.


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Hegyi M, Semsei AF, Jakab Z, Antal I, Kiss J, Szendroi M, et al. Good prognosis of localized osteosarcoma in young patients treated with limb-salvage surgery and chemotherapy. Pediatr Blood Cancer 2011; 57: 415–22. doi: 10.1002/pbc.23172

Aponte-Tinao L, Ayerza MA, Muscolo DL, Farfalli GL. Survival, recurrence, and function after epiphyseal preservation and allograft reconstruction in osteosarcoma of the knee. Clin Orthop Relat Res 2015; 473: 1789–96. doi: 10.1007/s11999-014-4028-5

Mattick JS. Non-coding RNAs: the architects of eukaryotic complexity. EMBO Rep 2001; 2: 986–91. doi: 10.1093/embo-reports/kve230

Cheng DF, Fan JJ, Ma Y, Zhou YR, Qin K, Shi MM, et al. LncRNA SNHG7 promotes pancreatic cancer proliferation through ID4 by sponging miR-342-3p. Cell Biosci 2019; 9: 28. doi: 10.1186/s13578-019-0290-2

Castro-Oropeza R, Melendez-Zajgla J, Maldonado V, Vazquez-Santillan K. The emerging role of lncRNAs in the regulation of cancer stem cells. Cell Oncol 2018; 41: 585–603. doi: 10.1007/s13402-018-0406-4

Prensner JR, Chinnaiyan AM. The emergence of lncRNAs in cancer biology. Cancer Discov 2011; 1: 391–407. doi: 10.1158/2159-8290.CD-11-0209

Wang Y, Jiang F, Xiong Y, Cheng X, Qiu Z, Song R. LncRNA TTN-AS1 sponges miR-376a-3p to promote colorectal cancer progression via upregulating KLF15. Life Sci 2019; 244: 116936. doi: 10.1016/j.lfs.2019.116936

Wu DM, Zheng ZH, Zhang YB, Fan SH, Zhang ZF, Wang YJ, et al. Down-regulated lncRNA DLX6-AS1 inhibits tumorigenesis through STAT3 signaling pathway by suppressing CADM1 promoter methylation in liver cancer stem cells. J Exp Clin Cancer Res 2019; 38: 237. doi: 10.1186/s13046-019-1239-3

Fu XD, Tian YF, Kuang WL, Wen SL, Guo W. Long non-coding RNA DLX6-AS1 silencing inhibits malignant phenotypes of gastric cancer cells. Exp Ther Med 2019; 17: 4715–22. doi: 10.3892/etm.2019.7521

Huang YJ, Ni R, Wang J, Liu Y. Knockdown of lncRNA DLX6-AS1 inhibits cell proliferation, migration and invasion while promotes apoptosis by downregulating PRR11 expression and upregulating miR-144 in non-small cell lung cancer. Biomed Pharmacother 2019; 109: 1851–9. doi: 10.1016/j.biopha.2018.09.151

An Y, Chen XM, Yang Y, Mo F, Jiang Y, Sun DL, et al. LncRNA DLX6-AS1 promoted cancer cell proliferation and invasion by attenuating the endogenous function of miR-181 b in pancreatic cancer. Cancer Cell Int 2018; 18: 143. doi: 10.1186/s12935-018-0643-7

You Q, Shi HY, Gong CF, Tian XY, Li S. Long non-coding RNA DLX6-AS1 acts as an oncogene by targeting miR-613 in ovarian cancer. Eur Rev Med Pharmacol Sci 2019; 23: 6429–35.

Bartel DP. MicroRNAs: genomics, biogenesis, mechanism, and function (Reprinted from Cell, vol 116, pg 281–297, 2004). Cell 2007; 131: 11–29. doi: 10.1016/S0092-8674(04)00045-5

Xie F, Xie G, Sun Q. Long noncoding RNA DLX6-AS1 promotes the progression in cervical cancer by targeting miR-16-5p/ARPP19 axis. Cancer Biother Radiopharm 2020; 35: 129–36. doi: 10.1089/cbr.2019.2960

Zhao P, Guan H, Dai Z, Ma Y, Zhao Y, Liu D. Long noncoding RNA DLX6-AS1 promotes breast cancer progression via miR-505-3p/RUNX2 axis. Eur J Pharmacol 2019; 865: 172778. doi: 10.1016/j.ejphar.2019.172778

Siegel RL, Miller KD, Jemal A. Cancer statistics, 2017. CA Cancer J Clin. 2017; 67: 7–30. doi: 10.3322/caac.21387

Karapetyan AR, Buiting C, Kuiper RA, Coolen MW. Regulatory roles for long ncRNA and mRNA. Cancers 2013; 5: 462–90. doi: 10.3390/cancers5020462

Yang L, Lin C, Jin C, Yang JC, Tanasa B, Li W, et al. lncRNA-dependent mechanisms of androgen-receptor-regulated gene activation programs. Nature 2013; 500: 598–602. doi: 10.1038/nature12451

Zhu Y, Tong Y, Wu J, Liu Y, Zhao M. Knockdown of LncRNA GHET1 suppresses prostate cancer cell proliferation by inhibiting HIF-1alpha/Notch-1 signaling pathway via KLF2. BioFactors 2019; 45: 364–73. doi: 10.1002/biof.1486

Morini M, Astigiano S, Gitton Y, Emionite L, Mirisola V, Levi G, et al. Mutually exclusive expression of DLX2 and DLX5/6 is associated with the metastatic potential of the human breast cancer cell line MDA-MB-231. BMC Cancer 2010; 10: 649. doi: 10.1186/1471-2407-10-649

Drabkin HA, Starkova J, Gemmill RM. A triad of NRP2, DLX and p53 proteins in lung cancer metastasis. Oncotarget 2017; 8: 96464–5. doi: 10.18632/oncotarget.22097

Li YL, Lu Y, Chen YL. Long non-coding RNA SNHG16 affects cell proliferation and predicts a poor prognosis in patients with colorectal cancer via sponging miR-200a-3p. Biosci Rep 2019; 39: BSR20182498. doi: 10.1042/BSR20182498

Wang XB, Lin YQ, Liu JG. Long non-coding RNA DLX6-AS1 promotes proliferation by acting as a ceRNA targeting miR-199a in cervical cancer. Mol Med Rep 2019; 19: 1248–55. doi: 10.3892/mmr.2018.9729

Rong D, Sun H, Li Z, Liu S, Dong C, Fu K, et al. An emerging function of circRNA-miRNAs-mRNA axis in human diseases. Oncotarget 2017; 8: 73271–81. doi: 10.18632/oncotarget.19154

Zhou FR, Pan ZP, Shen F, Huang LQ, Cui JH, Cai K, et al. Long noncoding RNA DLX6-AS1 functions as a competing endogenous RNA for miR-577 to promote malignant development of colorectal cancer. Eur Rev Med Pharmacol Sci 2019; 23: 3742–8.

Yang J, Ye Z, Mei D, Gu H, Zhang J. Long noncoding RNA DLX6-AS1 promotes tumorigenesis by modulating miR-497-5p/FZD4/FZD6/Wnt/beta-catenin pathway in pancreatic cancer. Cancer Manag Res 2019; 11: 4209–21. doi: 10.2147/CMAR.S194453

Zang YZ, Tai Y, Wan BL, Jia XD. miR-200a-3p promotes the proliferation of human esophageal cancer cells by post-transcriptionally regulating cytoplasmic collapsin response mediator protein-1. Int J Mol Med 2016; 38: 1558–64. doi: 10.3892/ijmm.2016.2758

Wu W, Wei N, Shao G, Jiang C, Zhang S, Wang L. circZNF609 promotes the proliferation and migration of gastric cancer by sponging miR-483-3p and regulating CDK6. OncoTargets Ther 2019; 12: 8197–205. doi: 10.2147/OTT.S193031

Wu DM, Wang S, Wen X, Han XR, Wang YJ, Shen M, et al. LncRNA SNHG15 acts as a ceRNA to regulate YAP1-Hippo signaling pathway by sponging miR-200a-3p in papillary thyroid carcinoma. Cell Death Dis 2018; 9: 947. doi: 10.1038/s41419-018-0975-1

Kuo WT, Yu SY, Li SC, Lam HC, Chang HT, Chen WS, et al. MicroRNA-324 in human cancer: miR-324-5p and miR-324-3p have distinct biological functions in human cancer. Anticancer Res 2016; 36: 5189–96. doi: 10.21873/anticanres.11089

Kim VN, Han J, Siomi MC. Biogenesis of small RNAs in animals. Nat Rev Mol Cell Biol 2009; 10: 126–39. doi: 10.1038/nrm2632

Charfi C, Edouard E, Rassart E. Identification of GPM6A and GPM6B as potential new human lymphoid leukemia-associated oncogenes. Cell Oncol 2014; 37: 179–91. doi: 10.1007/s13402-014-0171-y

Bilecova-Rabajdova M, Urban P, Gregova K, Varga J, Fialkovicova V, Kruzliak P, et al. Breast carcinoma progression and tumour vascular markers related to apoptotic mechanisms. Dis Markers 2014; 2014: 156034. doi: 10.1155/2014/156034

How to Cite
WuT., HuangC., & WangF. (2022). LncRNA DLX6-AS1 regulates osteosarcoma progression via the miR-200a-3p/GPM6P axis. STEMedicine, 3(1), e111. https://doi.org/10.37175/stemedicine.v3i1.111
Research articles