Long non‑coding RNA DANCR promotes HMGA2‑mediated invasion in lung adenocarcinoma cells

Zhang,Ningning; Jiang,Wei

doi:10.3892/or.2018.6897

Long non‑coding RNA DANCR promotes HMGA2‑mediated invasion in lung adenocarcinoma cells

Authors:
- Ningning Zhang
- Wei Jiang
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Affiliations: Youth League Committee, Central Hospital Affiliated to Shenyang Medical College, Shenyang, Liaoning 110024, P.R. China, Department of Thoracic Surgery, Central Hospital Affiliated to Shenyang Medical College, Shenyang, Liaoning 110024, P.R. China
Published online on: November 30, 2018 https://doi.org/10.3892/or.2018.6897
Pages: 1083-1090

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Abstract

Long non‑coding RNAs (lncRNAs) have been reported to be key regulators in various types of cancer, including lung adenocarcinoma (LAD). The roles of the lncRNA differentiation antagonizing non‑protein coding RNA (DANCR) and high mobility group AT‑hook 2 (HMGA2) in LAD remain unclear. In the present study, it was revealed that the lncRNA DANCR was upregulated in LAD tissue and cell lines, compared with para‑tumor tissue and a normal lung cell line. Additionally, elevated DANCR expression was associated with poor prognosis in the patients with LAD. Functionally, the study revealed that knockdown of DANCR inhibited invasion and HMGA2 expression in the LAD cell lines, SPCA1 and A549. Furthermore, HMGA2 was overexpressed in LAD tissue and in SPCA1 and A549 cells, compared with para‑tumor tissue and a normal lung cell line. Inhibition of HMGA2 suppressed the invasive ability of SPCA1 and A549 cells, and DANCR promoted the invasive ability via regulation of HMGA2 in SPCA1 and A549 cells. The findings of the present study revealed that DANCR promoted the invasion of LAD cells by positively regulating HMGA2. Thus, a DANCR/HMGA2 axis may be a novel potential target in the molecular treatment of LAD.

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1	Siegel RL, Miller KD and Jemal A: Cancer Statistics, 2017. CA Cancer J Clin. 67:7–30. 2017. View Article : Google Scholar : PubMed/NCBI
2	Abdeen Y, Amireh S, Patel A, Al-Halawani M, Shaaban H and Miller R: Cutaneous metastasis as a first presentation for lung adenocarcinoma. N Am J Med Sci. 8:222–225. 2016. View Article : Google Scholar : PubMed/NCBI
3	Dao A, Jabir H, Taleb A, Benchakroun N, Bouchbika Z, Nezha T, Jouhadi H, Sahraoui S and Benider A: Lung adenocarcinoma with thyroid metastasis: A case report. BMC Res Notes. 10:1302017. View Article : Google Scholar : PubMed/NCBI
4	Li H, Lian J, Han S, Wang W, Jia H, Cao J, Zhang X, Song X, Jia S, Ren J, et al: Applicability of graded prognostic assessment of lung cancer using molecular markers to lung adenocarcinoma patients with brain metastases. Oncotarget. 8:70727–70735. 2017.PubMed/NCBI
5	Yu M, Su Y, Cui D, Sun Q, Luan B and Zhao D: Chemotherapy effectively suppresses interleukin-20, receptor activator of nuclear factor kappa-B ligand, and osteoprotegerin levels in patients with lung adenocarcinoma and bone metastasis. J Cancer Res Ther. 12:963–968. 2016. View Article : Google Scholar : PubMed/NCBI
6	Behera M, Owonikoko TK, Gal AA, Steuer CE, Kim S, Pillai RN, Khuri FR, Ramalingam SS and Sica GL: Lung adenocarcinoma staging using the 2011 IASLC/ATS/ERS classification: A pooled analysis of adenocarcinoma in situ and minimally invasive adenocarcinoma. Clin Lung Cancer. 17:e57–e64. 2016. View Article : Google Scholar : PubMed/NCBI
7	Borczuk AC: Prognostic considerations of the new World Health Organization classification of lung adenocarcinoma. Eur Respir Rev. 25:364–371. 2016. View Article : Google Scholar : PubMed/NCBI
8	Chen B, Ma J, Li C and Wang Y: Long noncoding RNA KCNQ1OT1 promotes proliferation and epithelial-mesenchymal transition by regulation of SMAD4 expression in lens epithelial cells. Mol Med Rep. 18:16–24. 2018.PubMed/NCBI
9	Wang L, Ma L, Xu F, Zhai W, Dong S, Yin L, Liu J and Yu Z: Role of long non-coding RNA in drug resistance in non-small cell lung cancer. Thorac Cancer. 9:761–768. 2018. View Article : Google Scholar : PubMed/NCBI
10	Wang Y, Lu Z, Wang N, Feng J, Zhang J, Luan L, Zhao W and Zeng X: Long noncoding RNA DANCR promotes colorectal cancer proliferation and metastasis via miR-577 sponging. Exp Mol Med. 50:572018. View Article : Google Scholar : PubMed/NCBI
11	Wang Y, Zhang Y, Yang T, Zhao W, Wang N, Li P, Zeng X and Zhang W: Long non-coding RNA MALAT1 for promoting metastasis and proliferation by acting as a ceRNA of miR-144-3p in osteosarcoma cells. Oncotarget. 8:59417–59434. 2017.PubMed/NCBI
12	Wu X, Zheng Y, Han B and Dong X: Long noncoding RNA BLACAT1 modulates ABCB1 to promote oxaliplatin resistance of gastric cancer via sponging miR-361. Biomed Pharmacother. 99:832–838. 2018. View Article : Google Scholar : PubMed/NCBI
13	Jiang N, Wang X, Xie X, Liao Y, Liu N, Liu J, Miao N, Shen J and Peng T: lncRNA DANCR promotes tumor progression and cancer stemness features in osteosarcoma by upregulating AXL via miR-33a-5p inhibition. Cancer Lett. 405:46–55. 2017. View Article : Google Scholar : PubMed/NCBI
14	Ma X, Wang X, Yang C, Wang Z, Han B, Wu L and Zhuang L: DANCR Acts as a diagnostic biomarker and promotes tumor growth and metastasis in hepatocellular carcinoma. Anticancer Res. 36:6389–6398. 2016. View Article : Google Scholar : PubMed/NCBI
15	Pan L, Liang W, Gu J, Zang X, Huang Z, Shi H, Chen J, Fu M, Zhang P, Xiao X, et al: Long noncoding RNA DANCR is activated by SALL4 and promotes the proliferation and invasion of gastric cancer cells. Oncotarget. 9:1915–1930. 2017.PubMed/NCBI
16	Sha S, Yuan D, Liu Y, Han B and Zhong N: Targeting long non-coding RNA DANCR inhibits triple negative breast cancer progression. Biol Open. 6:1310–1316. 2017. View Article : Google Scholar : PubMed/NCBI
17	Lu QC, Rui ZH, Guo ZL, Xie W, Shan S and Ren T: lncRNA-DANCR contributes to lung adenocarcinoma progression by sponging miR-496 to modulate mTOR expression. J Cell Mol Med. 22:1527–1537. 2018. View Article : Google Scholar : PubMed/NCBI
18	Johnson KR, Lehn DA and Reeves R: Alternative processing of mRNAs encoding mammalian chromosomal high-mobility-group proteins HMG-I and HMG-Y. Mol Cell Biol. 9:2114–2123. 1989. View Article : Google Scholar : PubMed/NCBI
19	Pallante P, Sepe R, Puca F and Fusco A: High mobility group a proteins as tumor markers. Front Med (Lausanne). 2:152015.PubMed/NCBI
20	Chang HY, Ye SP, Pan SL, Kuo TT, Liu BC, Chen YL and Huang TC: Overexpression of miR-194 Reverses HMGA2-driven Signatures in Colorectal Cancer. Theranostics. 7:3889–3900. 2017. View Article : Google Scholar : PubMed/NCBI
21	Jiang C, Cao Y, Lei T, Wang Y, Fu J, Wang Z and Lv Z: microRNA-363-3p inhibits cell growth and invasion of non-small cell lung cancer by targeting HMGA2. Mol Med Rep. 17:2712–2718. 2018.PubMed/NCBI
22	Mei LL, Wang WJ, Qiu YT, Xie XF, Bai J and Shi ZZ: miR-125b-5p functions as a tumor suppressor gene partially by regulating HMGA2 in esophageal squamous cell carcinoma. PLoS One. 12:e01856362017. View Article : Google Scholar : PubMed/NCBI
23	Šamija I, Mateša N, Kožaj S, Majstorović I, Bolanča A and Kusić Z: HMGA2 gene expression in fine-needle aspiration samples of thyroid nodules as a marker for preoperative diagnosis of thyroid cancer. Appl Immunohistochem Mol Morphol. Feb 5–2018.(Epub ahead of print). doi: 10.1097/PAI.0000000000000637. View Article : Google Scholar :
24	Zhu J, Wang H, Xu S and Hao Y: Clinicopathological and prognostic significance of HMGA2 overexpression in gastric cancer: A meta-analysis. Oncotarget. 8:100478–100489. 2017.PubMed/NCBI
25	Zhuo HC, Song YF, Ye J, Lai GX and Liu DL: MicroRNA-154 functions as a tumor suppressor and directly targets HMGA2 in human non-small cell lung cancer. Genet Mol Res. 15:2016. View Article : Google Scholar :
26	Meyer B, Loeschke S, Schultze A, Weigel T, Sandkamp M, Goldmann T, Vollmer E and Bullerdiek J: HMGA2 overexpression in non-small cell lung cancer. Mol Carcinog. 46:503–511. 2007. View Article : Google Scholar : PubMed/NCBI
27	Xu L, Liao WL, Lu QJ, Li CG, Yuan Y, Xu ZY, Huang SD and Chen HZ: ANG promotes proliferation and invasion of the cell of lung squamous carcinoma by directly up-regulating HMGA2. J Cancer. 7:862–871. 2016. View Article : Google Scholar : PubMed/NCBI
28	Li X, Wang S, Li Z, Long X, Guo Z, Zhang G, Zu J, Chen Y and Wen L: The lncRNA NEAT1 facilitates cell growth and invasion via the miR-211/HMGA2 axis in breast cancer. Int J Biol Macromol. 105:346–353. 2017. View Article : Google Scholar : PubMed/NCBI
29	Wang Y, Zeng X, Wang N, Zhao W, Zhang X, Teng S, Zhang Y and Lu Z: Long noncoding RNA DANCR, working as a competitive endogenous RNA, promotes ROCK1-mediated proliferation and metastasis via decoying of miR-335-5p and miR-1972 in osteosarcoma. Mol Cancer. 17:892018. View Article : Google Scholar : PubMed/NCBI
30	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
31	Wang Y, Yang T, Liu Y, Zhao W, Zhang Z, Lu M and Zhang W: Decrease of miR-195 promotes chondrocytes proliferation and maintenance of chondrogenic phenotype via targeting FGF-18 pathway. Int J Mol Sci. 18(pii): E9752017. View Article : Google Scholar : PubMed/NCBI
32	Kretz M, Webster DE, Flockhart RJ, Lee CS, Zehnder A, Lopez-Pajares V, Qu K, Zheng GX, Chow J, Kim GE, et al: Suppression of progenitor differentiation requires the long noncoding RNA ANCR. Genes Dev. 26:338–343. 2012. View Article : Google Scholar : PubMed/NCBI
33	Liu X, Zheng J, Xue Y, Yu H, Gong W, Wang P, Li Z and Liu Y: PIWIL3/OIP5-AS1/miR-367-3p/CEBPA feedback loop regulates the biological behavior of glioma cells. Theranostics. 8:1084–1105. 2018. View Article : Google Scholar : PubMed/NCBI
34	Su R, Cao S, Ma J, Liu Y, Liu X, Zheng J, Chen J, Liu L, Cai H, Li Z, et al: Knockdown of SOX2OT inhibits the malignant biological behaviors of glioblastoma stem cells via up-regulating the expression of miR-194-5p and miR-122. Mol Cancer. 16:1712017. View Article : Google Scholar : PubMed/NCBI
35	Xu J, Ding R and Xu Y: Effects of long non-coding RNA SPRY4-IT1 on osteosarcoma cell biological behavior. Am J Transl Res. 8:5330–5337. 2016.PubMed/NCBI
36	Zhang L, Yang C, Chen S, Wang G, Shi B, Tao X, Zhou L and Zhao J: Long noncoding RNA DANCR is a positive regulator of proliferation and chondrogenic differentiation in human synovium-derived stem cells. DNA Cell Biol. 36:136–142. 2017. View Article : Google Scholar : PubMed/NCBI
37	Wang S and Jiang M: The long non-coding RNA-DANCR exerts oncogenic functions in non-small cell lung cancer via miR-758-3p. Biomed Pharmacother. 103:94–100. 2018. View Article : Google Scholar : PubMed/NCBI
38	Zhen Q, Gao LN, Wang RF, Chu WW, Zhang YX, Zhao XJ, Lv BL and Liu JB: lncRNA DANCR promotes lung cancer by sequestering miR-216a. Cancer Control. 25:10732748187698492018. View Article : Google Scholar : PubMed/NCBI
39	Cleynen I and Van de Ven WJ: The HMGA proteins: A myriad of functions (Review). Int J Oncol. 32:289–305. 2008.PubMed/NCBI
40	Sun J, Sun B, Zhu D, Zhao X, Zhang Y, Dong X, Che N, Li J, Liu F, Zhao N, et al: HMGA2 regulates CD44 expression to promote gastric cancer cell motility and sphere formation. Am J Cancer Res. 7:260–274. 2017.PubMed/NCBI
41	Fan C, Lin Y, Mao Y, Huang Z, Liu AY, Ma H, Yu D, Maitikabili A, Xiao H, Zhang C, et al: MicroRNA-543 suppresses colorectal cancer growth and metastasis by targeting KRAS, MTA1 and HMGA2. Oncotarget. 7:21825–21839. 2016.PubMed/NCBI
42	Yang E, Cisowski J, Nguyen N, O'Callaghan K, Xu J, Agarwal A, Kuliopulos A and Covic L: Dysregulated protease activated receptor 1 (PAR1) promotes metastatic phenotype in breast cancer through HMGA2. Oncogene. 35:1529–1540. 2016. View Article : Google Scholar : PubMed/NCBI
43	Gao X, Dai M, Li Q, Wang Z, Lu Y and Song Z: HMGA2 regulates lung cancer proliferation and metastasis. Thorac Cancer. 8:501–510. 2017. View Article : Google Scholar : PubMed/NCBI
44	Akhade VS, Pal D and Kanduri C: Long noncoding RNA: Genome organization and mechanism of action. Adv Exp Med Biol. 1008:47–74. 2017. View Article : Google Scholar : PubMed/NCBI