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Cancer Cell International
Published in: Cancer Cell International 1/2018

Open Access 01-12-2018 | Primary research

LncRNA DLX6-AS1 promoted cancer cell proliferation and invasion by attenuating the endogenous function of miR-181b in pancreatic cancer

Authors: Yong An, Xue-min Chen, Yong Yang, Feng Mo, Yong Jiang, Dong-lin Sun, Hui-hua Cai

Published in: Cancer Cell International | Issue 1/2018

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Abstract

Background

Pancreatic cancer, one of the most aggressive malignancies, ranks the fourth cause of cancer-related death worldwide. Aberrantly expressed long non-coding RNAs (lncRNAs) functioned as oncogenes or tumor suppressors in pancreatic cancer. This study aimed to determine the expression of lncRNA DLX6 antisense RNA 1 (DLX6-AS1) in pancreatic cancer tissues and to explore the DLX6-AS1-related pathway in pancreatic cancer.

Materials and methods

The gene expression levels were determined by quantitative real-time PCR, and protein expression levels were determined by western blot assay. CCK-8 assay, colony formation assay and Transwell migration and invasion assays were used to examine cell proliferation, migration and invasion. Luciferase reporter assay was used to confirm the binding between DLX6-AS1and its potential targets. In vivo study used the mouse xenograft model to test the anti-tumor effect of DLX6-AS1 knockdown.

Results

The high expression of DLX6-AS1 was observed in pancreatic cancer tissues, and high expression of DLX6-AS1 was positively correlated with larger tumor size, advanced TNM stage and lymph node metastasis. Knockdown of DLX6-AS1 dramatically impaired cancer cell proliferation, migration and invasion. MiR-181b was the downstream target of DLX6-AS1. Knockdown of miR-181b reversed the suppression of cell viability, migration and invasion abilities caused by DLX6-AS1 knockdown. MiR-181b was found to target Zinc finger E-box-binding homeobox 2 and to modulate epithelial-mesenchymal transition. Furthermore, DLX6-AS1 knockdown inhibited tumor growth and tumor metastasis in vivo.

Conclusion

Collectively, our data suggested that DLX6-AS1 promotes cancer cell proliferation and invasion by attenuating the endogenous function of miR-181b in pancreatic cancer.
Literature
1.
2.
Di Marco M, Grassi E, Durante S, Vecchiarelli S, Palloni A, Macchini M, Casadei R, Ricci C, Panzacchi R, Santini D, et al. State of the art biological therapies in pancreatic cancer. World J Gastrointest Oncol. 2016;8(1):55–66.CrossRefPubMed
3.
Kipps E, Young K, Starling N. Liposomal irinotecan in gemcitabine-refractory metastatic pancreatic cancer: efficacy, safety and place in therapy. Ther Adv Med Oncol. 2017;9(3):159–70.CrossRefPubMed
4.
Rajabpour A, Afgar A, Mahmoodzadeh H, Radfar JE, Rajaei F, Teimoori-Toolabi L. MiR-608 regulating the expression of ribonucleotide reductase M1 and cytidine deaminase is repressed through induced gemcitabine chemoresistance in pancreatic cancer cells. Cancer Chemother Pharmacol. 2017;80(4):765–75.CrossRefPubMed
5.
Kim E, Kim K, Kyu Chie E, Oh DY, Tae Kim Y. Chemoradiotherapy after gemcitabine plus erlotinib in patients with locally advanced pancreatic cancer. J BUON. 2017;22(4):1046–52.PubMed
6.
Djebali S, Davis CA, Merkel A, Dobin A, Lassmann T, Mortazavi A, Tanzer A, Lagarde J, Lin W, Schlesinger F, et al. Landscape of transcription in human cells. Nature. 2012;489(7414):101–8.CrossRefPubMed
7.
Gutschner T, Diederichs S. The hallmarks of cancer: a long non-coding RNA point of view. RNA Biol. 2012;9(6):703–19.CrossRefPubMed
8.
Ma L, Tian X, Guo H, Zhang Z, Du C, Wang F, Xie X, Gao H, Zhuang Y, Kornmann M, et al. Long noncoding RNA H19 derived miR-675 regulates cell proliferation by down-regulating E2F-1 in human pancreatic ductal adenocarcinoma. J Cancer. 2018;9(2):389–99.CrossRefPubMed
9.
Lian Y, Li Z, Fan Y, Huang Q, Chen J, Liu W, Xiao C, Xu H. The lncRNA-HOXA-AS2/EZH2/LSD1 oncogene complex promotes cell proliferation in pancreatic cancer. Am J Transl Res. 2017;9(12):5496–506.PubMedCentralPubMed
10.
Hayes J, Peruzzi PP, Lawler S. MicroRNAs in cancer: biomarkers, functions and therapy. Trends Mol Med. 2014;20(8):460–9.CrossRef
11.
Shah MY, Ferrajoli A, Sood AK, Lopez-Berestein G, Calin GA. microRNA therapeutics in cancer—an emerging concept. EBioMedicine. 2016;12:34–42.CrossRefPubMed
12.
Xie F, Huang Q, Liu CH, Lin XS, Liu Z, Liu LL, Huang DW, Zhou HC. MiR-1271 negatively regulates AKT/MTOR signaling and promotes apoptosis via targeting PDK1 in pancreatic cancer. Eur Rev Med Pharmacol Sci. 2018;22(3):678–86.PubMed
13.
Feng SD, Mao Z, Liu C, Nie YS, Sun B, Guo M, Su C. Simultaneous overexpression of miR-126 and miR-34a induces a superior antitumor efficacy in pancreatic adenocarcinoma. OncoTargets Ther. 2017;10:5591–604.CrossRef
14.
Li J, Li P, Zhao W, Yang R, Chen S, Bai Y, Dun S, Chen X, Du Y, Wang Y, et al. Expression of long non-coding RNA DLX6-AS1 in lung adenocarcinoma. Cancer Cell Int. 2015;15:48.CrossRefPubMed
15.
Li L, Hou A, Gao X, Zhang J, Zhang L, Wang J, Li H, Song Y. Lentivirus-mediated miR-23a overexpression induces trophoblast cell apoptosis through inhibiting X-linked inhibitor of apoptosis. Biomed Pharmacother. 2017;94:412–7.CrossRefPubMed
16.
17.
18.
Vincent A, Herman J, Schulick R, Hruban RH, Goggins M. Pancreatic cancer. Lancet. 2011;378(9791):607–20.CrossRefPubMed
19.
Wang L, Wang F, Na L, Yu J, Huang L, Meng ZQ, Chen Z, Chen H, Ming LL, Hua YQ. LncRNA AB209630 inhibits gemcitabine resistance cell proliferation by regulating PI3K/AKT signaling in pancreatic ductal adenocarcinoma. Cancer Biomark. 2018;22(1):169–74.CrossRefPubMed
20.
Zhang M, Zhao Y, Zhang Y, Wang D, Gu S, Feng W, Peng W, Gong A, Xu M. LncRNA UCA1 promotes migration and invasion in pancreatic cancer cells via the Hippo pathway. Biochimica et biophysica acta. 2018;1864(5 Pt A):1770–82.CrossRefPubMed
21.
Hu H, Wang Y, Ding X, He Y, Lu Z, Wu P, Tian L, Yuan H, Liu D, Shi G, et al. Long non-coding RNA XLOC_000647 suppresses progression of pancreatic cancer and decreases epithelial-mesenchymal transition-induced cell invasion by down-regulating NLRP3. Mol Cancer. 2018;17(1):18.CrossRefPubMed
22.
Liu YS, Lin HY, Lai SW, Huang CY, Huang BR, Chen PY, Wei KC, Lu DY. MiR-181b modulates EGFR-dependent VCAM-1 expression and monocyte adhesion in glioblastoma. Oncogene. 2017;36(35):5006–22.CrossRefPubMed
23.
Li JG, Ding Y, Huang YM, Chen WL, Pan LL, Li Y, Chen XL, Chen Y, Wang SY, Wu XN. FAMLF is a target of miR-181b in Burkitt lymphoma. Braz J Med Biol Res. 2017;50(6):e5661.PubMedCentralPubMed
24.
Wang L, Wang YX, Chen LP, Ji ML. Upregulation of microRNA-181b inhibits CCL18-induced breast cancer cell metastasis and invasion via the NF-kappaB signaling pathway. Oncol Lett. 2016;12(6):4411–8.CrossRefPubMed
25.
Lim J, Thiery JP. Epithelial-mesenchymal transitions: insights from development. Development. 2012;139(19):3471–86.CrossRefPubMed
26.
Tam WL, Weinberg RA. The epigenetics of epithelial-mesenchymal plasticity in cancer. Nat Med. 2013;19(11):1438–49.CrossRefPubMed
27.
Zhu GJ, Song PP, Zhou H, Shen XH, Wang JG, Ma XF, Gu YJ, Liu DD, Feng AN, Qian XY, et al. Role of epithelial-mesenchymal transition markers E-cadherin, N-cadherin, beta-catenin and ZEB2 in laryngeal squamous cell carcinoma. Oncol Lett. 2018;15(3):3472–81.PubMedCentralPubMed
28.
Wang T, Chen X, Qiao W, Kong L, Sun D, Li Z. Transcription factor E2F1 promotes EMT by regulating ZEB2 in small cell lung cancer. BMC Cancer. 2017;17(1):719.CrossRefPubMed
Metadata
Title
LncRNA DLX6-AS1 promoted cancer cell proliferation and invasion by attenuating the endogenous function of miR-181b in pancreatic cancer
Authors
Yong An
Xue-min Chen
Yong Yang
Feng Mo
Yong Jiang
Dong-lin Sun
Hui-hua Cai
Publication date
01-12-2018
Publisher
BioMed Central
Published in
Cancer Cell International / Issue 1/2018
Electronic ISSN: 1475-2867
DOI
https://doi.org/10.1186/s12935-018-0643-7

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