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DLX6-AS1: a putative lncRNA candidate in multiple human cancers

Published online by Cambridge University Press:  26 November 2021

Mohsen Sheykhhasan Open the ORCID record for Mohsen Sheykhhasan [Opens in a new window] ,
Yaghoub Ahmadyousefi ,
Reihaneh Seyedebrahimi ,
Hamid Tanzadehpanah ,
Hamed Manoochehri ,
Paola Dama ,
Nashmin Fayazi Hosseini ,
Mohammad Akbari  and
Mohsen Eslami Farsani Open the ORCID record for Mohsen Eslami Farsani [Opens in a new window]
Mohsen Sheykhhasan*
Affiliation:
Department of Molecular Medicine and Genetics, Research Center for Molecular Medicine, Hamadan University of Medical Sciences, Hamadan, Iran
Yaghoub Ahmadyousefi
Affiliation:
Department of Molecular Medicine and Genetics, Research Center for Molecular Medicine, Hamadan University of Medical Sciences, Hamadan, Iran
Reihaneh Seyedebrahimi
Affiliation:
Anatomy Department, Faculty of Medicine, Qom University of Medical Sciences, Qom, Iran
Hamid Tanzadehpanah
Affiliation:
Department of Molecular Medicine and Genetics, Research Center for Molecular Medicine, Hamadan University of Medical Sciences, Hamadan, Iran
Hamed Manoochehri
Affiliation:
Department of Molecular Medicine and Genetics, Research Center for Molecular Medicine, Hamadan University of Medical Sciences, Hamadan, Iran
Paola Dama
Affiliation:
Molecular Oncology and Pharmacology, School of Life Sciences, University of Sussex, Brighton, UK
Nashmin Fayazi Hosseini
Affiliation:
Department of Molecular Medicine and Genetics, Research Center for Molecular Medicine, Hamadan University of Medical Sciences, Hamadan, Iran
Mohammad Akbari
Affiliation:
General Physician, Department of Medical School, Faculty of Medical Sciences, Islamic Azad University, Tonekabon Branch, Mazandaran, Iran
Mohsen Eslami Farsani
Affiliation:
Anatomy Department, Faculty of Medicine, Qom University of Medical Sciences, Qom, Iran Cellular and Molecular Research Center, Qom University of Medical Sciences, Qom, Iran
*
Author for correspondence: Mohsen Sheykhhasan, E-mail: [email protected]
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Abstract

Long non-coding RNAs (lncRNAs) have important roles in regulating the expression of genes and act as biomarkers in the initial development of different cancers. Increasing research studies have verified that dysregulation of lncRNAs occurs in various pathological processes including tumorigenesis and cancer progression. Among the different lncRNAs, DLX6-AS1 has been reported to act as an oncogene in the development and prognoses of different cancers, by affecting many different signalling pathways. This review summarises and analyses the recent research studies describing the biological functions of DLX6-AS1, its overall effect on signalling pathways and the molecular mechanisms underlying its action on the expression of genes in multiple human cancers. Our critical analysis suggests that different signalling pathways associated to this lncRNA may be used as a biomarker for diagnosis, or targets of treatment in cancers.

Keywords

Cancer biomarkerdiagnosisDLX6-AS1long non-coding RNANeoplasmtreatment target
Type
Review
Information
Expert Reviews in Molecular Medicine , Volume 23 , 2021 , e17
Copyright
Copyright © The Author(s), 2021. Published by Cambridge University Press

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Footnotes

*

These authors contributed equally.

References

Bray, F et al. (2018) Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA: A Cancer Journal for Clinicians 68, 394–424.Google ScholarPubMed
Liu, L et al. (2020) Noncoding RNAs: the shot callers in tumor immune escape. Signal Transduction and Targeted Therapy 5, 1–24.CrossRefGoogle ScholarPubMed
Huang, T et al. (2013) Noncoding RNAs in cancer and cancer stem cells. Chinese Journal of Cancer 32, 582.CrossRefGoogle ScholarPubMed
Chi, Y et al. (2019) Long non-coding RNA in the pathogenesis of cancers. Cells 8, 1015.CrossRefGoogle ScholarPubMed
Hosseini, NF et al. (2021) The functional role of long non-coding RNA UCA1 in human multiple cancers: a review study. Current Molecular Medicine 21, 96–110.CrossRefGoogle ScholarPubMed
Ji, Z et al. (2015) Many lncRNAs, 5’UTRs, and pseudogenes are translated and some are likely to express functional proteins. Elife 4, e08890.CrossRefGoogle ScholarPubMed
Matsumoto, A et al. (2017) mTORC1 and muscle regeneration are regulated by the LINC00961-encoded SPAR polypeptide. Nature 541, 228–232.CrossRefGoogle ScholarPubMed
Zhou, B et al. (2021) Translation of noncoding RNAs and cancer. Cancer Letters 497, 89–99.CrossRefGoogle ScholarPubMed
Bhat, SA et al. (2016) Long non-coding RNAs: mechanism of action and functional utility. Non-Coding RNA Research 1, 43–50.CrossRefGoogle ScholarPubMed
Mao, YS et al. (2011) Direct visualization of the co-transcriptional assembly of a nuclear body by noncoding RNAs. Nature Cell Biology 13, 95–101.CrossRefGoogle ScholarPubMed
Fejes-Toth, K et al. (2009) Post-transcriptional processing generates a diversity of 5′-modified long and short RNAs: affymetrix/Cold Spring Harbor laboratory ENCODE transcriptome project. Nature 457, 1028.Google Scholar
Zhao, J et al. (2008) Polycomb proteins targeted by a short repeat RNA to the mouse X chromosome. Science 322, 750–756.CrossRefGoogle ScholarPubMed
Sado, T, Hoki, Y and Sasaki, H (2005) Tsix silences Xist through modification of chromatin structure. Developmental Cell 9, 159–165.CrossRefGoogle ScholarPubMed
Blume, SW et al. (2003) The 5′-untranslated RNA of the human dhfr minor transcript alters transcription pre-initiation complex assembly at the major (core) promoter. Journal of Cellular Biochemistry 88, 165–180.CrossRefGoogle Scholar
Martianov, I et al. (2007) Repression of the human dihydrofolate reductase gene by a non-coding interfering transcript. Nature 445, 666–670.CrossRefGoogle ScholarPubMed
He, Y et al. (2014) Long noncoding RNAs: novel insights into hepatocelluar carcinoma. Cancer Letters 344, 20–27.CrossRefGoogle ScholarPubMed
Jin, K-T et al. (2020) Roles of lncRNAs in cancer: focusing on angiogenesis. Life Sciences 252, 117647.CrossRefGoogle ScholarPubMed
Wapinski, O and Chang, HY (2011) Long noncoding RNAs and human disease. Trends in Cell Biology 21, 354–361.CrossRefGoogle ScholarPubMed
Clark, MB and Mattick, JS (2011) Long noncoding RNAs in cell biology. Seminars in Cell & Developmental Biology 22, 366–376.CrossRefGoogle ScholarPubMed
Arun, G, Diermeier, SD and Spector, DL (2018) Therapeutic targeting of long non-coding RNAs in cancer. Trends in Molecular Medicine 24, 257–277.CrossRefGoogle ScholarPubMed
Lu, G et al. (2018) Long noncoding RNA LINC00511 contributes to breast cancer tumourigenesis and stemness by inducing the miR-185-3p/E2F1/Nanog axis. Journal of Experimental & Clinical Cancer Research 37, 289.CrossRefGoogle Scholar
Martens-Uzunova, ES et al. (2014) Long noncoding RNA in prostate, bladder, and kidney cancer. European urology 65, 1140–1151.CrossRefGoogle ScholarPubMed
Yang, G, Lu, X and Yuan, L (2014) LncRNA: a link between RNA and cancer. Biochimica et Biophysica Acta (BBA)-Gene Regulatory Mechanisms 1839, 1097–1109.CrossRefGoogle ScholarPubMed
Zhang, R et al. (2016) LncRNAs and cancer. Oncology Letters 12, 1233–1239.CrossRefGoogle ScholarPubMed
Sun, W et al. (2019) LncRNA DLX6-AS1 promotes the proliferation, invasion, and migration of non-small cell lung cancer cells by targeting the miR-27b-3p/GSPT1 axis. OncoTargets and therapy 12, 3945–3954.CrossRefGoogle ScholarPubMed
Li, J et al. (2015) Expression of long non-coding RNA DLX6-AS1 in lung adenocarcinoma. Cancer Cell International 15, 48.CrossRefGoogle ScholarPubMed
Guo, J et al. (2019) The lncRNA DLX6-AS1 promoted cell proliferation, invasion, migration and epithelial-to-mesenchymal transition in bladder cancer via modulating Wnt/β-catenin signaling pathway. Cancer Cell International 19, 1–11.CrossRefGoogle ScholarPubMed
Fang, C et al. (2019) Long noncoding RNA DLX6-AS1 promotes cell growth and invasiveness in bladder cancer via modulating the miR-223-HSP90B1 axis. Cell Cycle 18, 3288–3299.CrossRefGoogle ScholarPubMed
Xie, F et al. (2020) Long Noncoding RNA DLX6-AS1 Promotes the Progression in Cervical Cancer by Targeting miR-16-5p/ARPP19 Axis.CrossRefGoogle Scholar
Zhao, P et al. (2019) Long noncoding RNA DLX6-AS1 promotes breast cancer progression via miR-505-3p/RUNX2 axis. European Journal of Pharmacology 865, 172778.CrossRefGoogle ScholarPubMed
Wang, P et al. (2020) Long noncoding RNA DLX6-AS1 promotes migration and invasion of breast cancer cells by upregulating FUS. Panminerva Medica.Google ScholarPubMed
Liu, S et al. (2020) ceRNA Network Development and Tumour-infiltrating Immune Cell Analysis in Metastatic Breast Cancer of Bone.CrossRefGoogle Scholar
Du, C et al. (2020) LncRNA DLX6-AS1 contributes to epithelial–mesenchymal transition and cisplatin resistance in triple-negative breast cancer via modulating Mir-199b-5p/paxillin axis. Cell Transplant 29, 0963689720929983.CrossRefGoogle ScholarPubMed
Wang, X, Lin, Y and Liu, J (2019) Long non-coding RNA DLX6-AS1 promotes proliferation by acting as a ceRNA targeting miR-199a in cervical cancer. Molecular Medicine Reports 19, 1248–1255.Google Scholar
Zhang, J et al. (2019) The up-regulated lncRNA DLX6-AS1 in colorectal cancer promotes cell proliferation, invasion and migration via modulating PI3 K/AKT/mTOR pathway. European Review for Medical and Pharmacological Sciences 23, 8321–8331.Google Scholar
Kong, W-Q et al. (2021) Long noncoding RNA DLX6-AS1 regulates the growth and aggressiveness of colorectal cancer cells Via mediating miR-26a/EZH2 axis. Cancer Biotherapy & Radiopharmaceuticals 36, 753–764.CrossRefGoogle ScholarPubMed
Zhao, H and Xu, Q. (2020) Long non-coding RNA DLX6-AS1 mediates proliferation, invasion and apoptosis of endometrial cancer cells by recruiting p300/E2F1 in DLX6 promoter region. Journal of Cellular and Molecular Medicine 24, 12572–12584.CrossRefGoogle Scholar
Zhao, J and Liu, HR (2019) Down-regulation of long noncoding RNA DLX6-AS1 defines good prognosis and inhibits proliferation and metastasis in human epithelial ovarian cancer cells via notch signaling pathway. European Review for Medical and Pharmacological Sciences 23, 3243–3252.Google ScholarPubMed
Wang, M et al. (2019) Long non-coding RNA DLX6-AS1 is associated with malignant progression and promotes proliferation and invasion in esophageal squamous cell carcinoma. Molecular Medicine Reports 19, 1942–1950.Google Scholar
Tian, W et al. (2019) Comprehensive analysis of dysregulated lncRNAs, miRNAs and mRNAs with associated ceRNA network in esophageal squamous cell carcinoma. Gene 696, 206–218.CrossRefGoogle ScholarPubMed
Lijie, Y, Xinxin, T and Zhenjie, G (2020) The molecular mechanism of long non-coding RNA DLX6-AS1 regulating microRNA-15b and phospholipase D1 affecting the invasion and metastasis of oral squamous cell carcinoma. Journal of Oral and Maxillofacial Surgery 30, 222.Google Scholar
Lei, X et al. (2019) Long noncoding RNA DLX6-AS1 targets miR-124-3p/CDK4 to accelerate ewing's sarcoma. American Journal of Translational Research 11, 6569–6576.Google ScholarPubMed
Fu, X et al. (2019) Long non-coding RNA DLX6-AS1 silencing inhibits malignant phenotypes of gastric cancer cells. Experimental and Therapeutic Medicine 17, 4715–4722.Google ScholarPubMed
Wu, Q et al. (2020) DLX6-AS1 Promotes cell proliferation, migration and EMT of gastric cancer through FUS-regulated MAP4K1. Cancer Biology & Therapy 21, 17–25.CrossRefGoogle ScholarPubMed
Liang, Y et al. (2020) DLX6-AS1/miR-204-5p/OCT1 Positive feedback loop promotes tumor progression and epithelial–mesenchymal transition in gastric cancer. Gastric Cancer: Official Journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association 23, 212–227.CrossRefGoogle ScholarPubMed
Qian, Y et al. (2021) DLX6 Antisense RNA 1 modulates glucose metabolism and cell growth in gastric cancer by targeting microRNA-4290. Digestive Diseases and Sciences 66, 460–473.CrossRefGoogle ScholarPubMed
Li, X, Zhang, H and Wu, X (2019) Long noncoding RNA DLX6-AS1 accelerates the glioma carcinogenesis by competing endogenous sponging miR-197-5p to relieve E2F1. Gene 686, 1–7.CrossRefGoogle ScholarPubMed
Zhang, L et al. (2017) Long non-coding RNA DLX6-AS1 aggravates hepatocellular carcinoma carcinogenesis by modulating miR-203a/MMP-2 pathway. Biomedicine & Pharmacotherapy 96, 884–891.CrossRefGoogle ScholarPubMed
Wu, D-M et al. (2019) Down-regulated lncRNA DLX6-AS1 inhibits tumorigenesis through STAT3 signaling pathway by suppressing CADM1 promoter methylation in liver cancer stem cells. Journal of Experimental & Clinical Cancer Research 38, 237.CrossRefGoogle ScholarPubMed
Liu, Y et al. (2020) lncRNA DLX6-AS1 promotes proliferation of laryngeal cancer cells by targeting the miR-26a/TRPC3 pathway. Cancer Management and Research 12, 2685.CrossRefGoogle ScholarPubMed
Yang, Q et al. (2019) LncRNA DLX6-AS1 promotes laryngeal squamous cell carcinoma growth and invasion through regulating miR-376c. American Journal of Translational Research 11, 7009.Google ScholarPubMed
Li, D et al. (2019) Long noncoding RNA DLX6-AS1 promotes liver cancer by increasing the expression of WEE1 via targeting miR-424-5p. Journal of Cellular Biochemistry 120, 12290–12299.CrossRefGoogle ScholarPubMed
Yao, Y et al. (2019) Competitive endogenous RNA network construction and comparison of lung squamous cell carcinoma in smokers and nonsmokers. Disease Markers 2019, 1–14.Google ScholarPubMed
Yang, B et al. (2020) LncRNA DLX6-AS1 increases the expression of HIF-1α and promotes the malignant phenotypes of nasopharyngeal carcinoma cells via targeting MiR-199a-5p. Molecular Genetics & Genomic Medicine 8, e1017.CrossRefGoogle ScholarPubMed
Zhang, H-Y et al. (2019) Long noncoding RNA DLX6-AS1 promotes neuroblastoma progression by regulating miR-107/BDNF pathway. Cancer Cell International 19, 313.CrossRefGoogle ScholarPubMed
Li, C, Wang, S and Yang, C (2020) Long non-coding RNA DLX6-AS1 regulates neuroblastoma progression by targeting YAP1 via miR-497-5p. Life Sciences 252, 117657.CrossRefGoogle ScholarPubMed
Hu, Y et al. (2020) lncRNA DLX6-AS1 promotes the progression of neuroblastoma by activating STAT2 via targeting miR-506-3p. Cancer Management and Research 12, 7451.CrossRefGoogle ScholarPubMed
Jia, P et al. Silencing of long non-coding RNA DLX6-AS1 weakens neuroblastoma progression by the miR-513c-5p/PLK4 axis. IUBMB Life 72, 2627–2636.CrossRefGoogle Scholar
Zhang, X et al. (2019) Exosomal long non-coding RNA DLX6-AS1 as a potential diagnostic biomarker for non-small cell lung cancer. Oncology Letters 18, 5197–5204.Google ScholarPubMed
Huang, Y et al. (2019) 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. Biomedicine & Pharmacotherapy 109, 1851–1859.CrossRefGoogle ScholarPubMed
Zhang, N et al. (2019) LncRNA DLX6-AS1 promotes tumor proliferation and metastasis in osteosarcoma through modulating miR-641/HOXA9 signaling pathway. Journal of Cellular Biochemistry 120, 11478–11489.CrossRefGoogle Scholar
Zhang, R-M et al. (2018) LncRNA DLX6-AS1/miR-129-5p/DLK1 axis aggravates stemness of osteosarcoma through Wnt signaling. Biochemical and Biophysical Research Communications 507, 260–266.CrossRefGoogle ScholarPubMed
Kong, L and Zhang, CJCCI (2020) LncRNA DLX6-AS1 aggravates the development of ovarian cancer via modulating FHL2 by sponging miR-195-5p. Cancer Cell International 20, 1–12.CrossRefGoogle Scholar
Zhang, M et al. (2020) Characterization of BRCA1/2-directed ceRNA network identifies a novel three-lncRNA signature to predict prognosis and chemo-response in ovarian cancer patients with wild-type BRCA1/2. Frontiers in Cell and Developmental Biology 8, 680.CrossRefGoogle ScholarPubMed
An, Y et al. (2018) LncRNA DLX6-AS1 promoted cancer cell proliferation and invasion by attenuating the endogenous function of miR-181b in pancreatic cancer. Cancer Cell International 18, 143.CrossRefGoogle ScholarPubMed
Yang, J et al. (2019) Long noncoding RNA DLX6-AS1 promotes tumorigenesis by modulating miR-497-5p/FZD4/FZD6/Wnt/beta-catenin pathway in pancreatic cancer. Cancer Management and Research 11, 4209–4221.CrossRefGoogle ScholarPubMed
Le, W et al. MiR-504 and miR-205 May be Used to Evaluate Prognosis and Chemotherapeutic Effect of Pancreatic Cancer Patients.Google Scholar
Weiss, M (2018) Identification and mechanistic characterization of DLX6-AS1 lncRNA in prostate cancer. In.Google Scholar
Zhao, Z, Liang, S and Sun, F (2020) LncRNA DLX6-AS1 promotes malignant phenotype and lymph node metastasis in prostate cancer by inducing LARGE methylation. Frontiers in Oncology 10, 1172.CrossRefGoogle ScholarPubMed
Zhu, X et al. (2021) DLX6-AS1 Accelerates cell proliferation through regulating miR-497-5p/SNCG pathway in prostate cancer. Environmental Toxicology 36, 308–319.CrossRefGoogle Scholar
Zeng, X et al. (2017) Long noncoding RNA DLX6-AS1 promotes renal cell carcinoma progression via miR-26a/PTEN axis. Cell Cycle 16, 2212–2219.CrossRefGoogle ScholarPubMed
Feng, L et al. (2021) Silencing long non-coding RNA DLX6-AS1 or restoring microRNA-193b-3p enhances thyroid carcinoma cell autophagy and apoptosis via depressing HOXA1. Journal of Cellular and Molecular Medicine 25, 9319–9330.CrossRefGoogle ScholarPubMed
Wang, H et al. . (2020) Long non-coding RNA DLX6-AS1 facilitates bladder cancer progression through modulating miR-195-5p/VEGFA signaling pathway. Aging (Albany NY) 12, 16021–16034.CrossRefGoogle Scholar
Liu, X et al. (2021) Upregulated lncRNA DLX6-AS1 underpins hepatocellular carcinoma progression via the miR-513c/Cul4A/ANXA10 axis. Cancer Gene Therapy 28, 486–501.CrossRefGoogle ScholarPubMed
Gertler, R et al. (2011) Long-term outcome of 2920 patients with cancers of the esophagus and esophagogastric junction: evaluation of the new union internationale contre le cancer/American joint cancer committee staging system. Annals of Surgery 253, 689–698.CrossRefGoogle ScholarPubMed
Zhang, J et al. Identification and Validation of an 8-lncRNA Signature That Predicts Prognosis in Patients With Esophageal Squamous Cell Carcinoma. Available at SSRN 3822287.Google Scholar
Chen, PJ et al. (2010) Issues and controversies of hepatocellular carcinoma-targeted therapy clinical trials in Asia: experts' opinion. Liver International 30, 1427–1438.CrossRefGoogle ScholarPubMed
Junyu, L (2019) Comprehensive analysis of hepatocellular carcinoma prognostic markers based on bioinformatics. Chinese Academy of Medical Sciences Peking Union Medical College Hospital, 1–10.Google Scholar
Wang, LP et al. (2021) Exosomal DLX6-AS1 from hepatocellular carcinoma cells induces M2 macrophage polarization to promote migration and invasion in hepatocellular carcinoma through microRNA-15a-5p/CXCL17 axis. Journal of Experimental & Clinical Cancer Research: CR 40, 177.CrossRefGoogle ScholarPubMed
Rawla, P, Sunkara, T and Gaduputi, V (2019) Epidemiology of pancreatic cancer: global trends, etiology and risk factors. World Journal of Oncology 10, 10.CrossRefGoogle ScholarPubMed
Steuer, CE et al. (2017) An update on larynx cancer. CA: a Cancer Journal for Clinicians 67, 31–50.Google ScholarPubMed
Huan, J et al. (2017) Long noncoding RNA CRNDE activates Wnt/β-catenin signaling pathway through acting as a molecular sponge of microRNA-136 in human breast cancer. American Journal of Translational Research 9, 1977.Google ScholarPubMed
Arbyn, M et al. (2020) Estimates of incidence and mortality of cervical cancer in 2018: a worldwide analysis. The Lancet Global Health 8, e191–e203.CrossRefGoogle ScholarPubMed
Yu, Y et al. (2018) LncRNA HCP5 promotes the development of cervical cancer by regulating MACC1 via suppression of microRNA-15a. European Review for Medical and Pharmacological Sciences 22, 4812–4819.Google ScholarPubMed
Lee, M et al. (2016) The long non-coding RNA HOTAIR increases tumour growth and invasion in cervical cancer by targeting the notch pathway. Oncotarget 7, 44558.CrossRefGoogle Scholar
Ding, XZ et al. (2021) Serum exosomal lncRNA DLX6-AS1 Is a promising biomarker for prognosis prediction of cervical cancer. Technology in Cancer Research & Treatment 20, 1533033821990060.CrossRefGoogle ScholarPubMed
Li, M et al. (2017) Long non-coding RNAs in renal cell carcinoma: a systematic review and clinical implications. Oncotarget 8, 48424.CrossRefGoogle ScholarPubMed
Cattrini, C and Boccardo, F (2018) Atezolizumab and bladder cancer: facing a complex disease. The Lancet 391, 305–306.CrossRefGoogle ScholarPubMed
Colon, NC and Chung, DH (2011) Neuroblastoma. Advances in Pediatrics 58, 297–311.CrossRefGoogle ScholarPubMed
Matheson, CJ, Backos, DS and Reigan, P (2016) Targeting WEE1 kinase in cancer. Trends in Pharmacological Sciences 37, 872–881.CrossRefGoogle ScholarPubMed