LncRNA DSCAM-AS1: A Pivotal Therapeutic Target in Cancer

Chengyu      Hu

Abstract

Background: LncRNAs are an emerging category of non-coding RNAs. LncRNAs are usually greater than 200 nucleotides in length and do not possess protein editing capabilities. DSCAM-AS1 is a highly valued member of the lncRNAs family. Numerous studies have revealed the involvement of the oncogene DSCAM-AS1 in multiple biological processes, including metastasis, aggressiveness and cell proliferation. This review discusses the molecular mechanisms and clinical significance of DSCAM-AS1 in various tumor types.

Methods: This paper analyzes and summarizes current research by searching PubMed using “DSCAM-AS1” and “tumor” as keywords.

Results: DSCAM-AS1 is a valuable tumor-associated lncRNA with significant oncogenic effects. It is abnormally expressed in a variety of cancers, such as non-small cell lung cancer, cervical cancer, osteosarcoma, colorectal cancer, breast cancer, gastric cancer and endometrial cancer. The overexpression of DSCAM-AS1 promotes cancer progression by modulating cancer cell proliferation, invasion, distant metastasis, and resistance.

Conclusion: DSCAM-AS1 is upregulated and acts as an oncogene in multiple tumors. As more systematic studies are performed, DSCAM-AS1 may prove to be a promising therapeutic target or tumor biomarker.

Keywords: Long noncoding RNA, DSCAM-AS1, tumorigenesis, tumor biomarker, therapeutic target, molecular mechanisms, oncogene.

Graphical Abstract

[1]
Johnsson, P.; Lipovich, L.; Grandér, D.; Morris, K.V. Evolutionary conservation of long non-coding RNAs; sequence, structure, function. Biochim. Biophys. Acta,  2014, 1840(3), 1063-1071.
 [http://dx.doi.org/10.1016/j.bbagen.2013.10.035] [PMID: 24184936]

[2]
Djebali, S.; Davis, C.A.; Merkel, A.; Dobin, A.; Lassmann, T.; Mortazavi, A.; Tanzer, A.; Lagarde, J.; Lin, W.; Schlesinger, F.; Xue, C.; Marinov, G.K.; Khatun, J.; Williams, B.A.; Zaleski, C.; Rozowsky, J.; Röder, M.; Kokocinski, F.; Abdelhamid, R.F.; Alioto, T.; Antoshechkin, I.; Baer, M.T.; Bar, N.S.; Batut, P.; Bell, K.; Bell, I.; Chakrabortty, S.; Chen, X.; Chrast, J.; Curado, J.; Derrien, T.; Drenkow, J.; Dumais, E.; Dumais, J.; Duttagupta, R.; Falconnet, E.; Fastuca, M.; Fejes-Toth, K.; Ferreira, P.; Foissac, S.; Fullwood, M.J.; Gao, H.; Gonzalez, D.; Gordon, A.; Gunawardena, H.; Howald, C.; Jha, S.; Johnson, R.; Kapranov, P.; King, B.; Kingswood, C.; Luo, O.J.; Park, E.; Persaud, K.; Preall, J.B.; Ribeca, P.; Risk, B.; Robyr, D.; Sammeth, M.; Schaffer, L.; See, L.H.; Shahab, A.; Skancke, J.; Suzuki, A.M.; Takahashi, H.; Tilgner, H.; Trout, D.; Walters, N.; Wang, H.; Wrobel, J.; Yu, Y.; Ruan, X.; Hayashizaki, Y.; Harrow, J.; Gerstein, M.; Hubbard, T.; Reymond, A.; Antonarakis, S.E.; Hannon, G.; Giddings, M.C.; Ruan, Y.; Wold, B.; Carninci, P.; Guigó, R.; Gingeras, T.R. Landscape of transcription in human cells. Nature,  2012, 489(7414), 101-108.
 [http://dx.doi.org/10.1038/nature11233] [PMID: 22955620]

[3]
Tano, K.; Akimitsu, N. Long non-coding RNAs in cancer progression. Front. Genet.,  2012, 3, 219.
 [http://dx.doi.org/10.3389/fgene.2012.00219] [PMID: 23109937]

[4]
Rinn, J.L.; Chang, H.Y. Genome regulation by long noncoding RNAs. Annu. Rev. Biochem.,  2012, 81, 145-166.
 [http://dx.doi.org/10.1146/annurev-biochem-051410-092902] [PMID: 22663078]

[5]
Bergmann, J.H.; Spector, D.L. Long non-coding RNAs: Modulators of nuclear structure and function. Curr. Opin. Cell Biol.,  2014, 26, 10-18.
 [http://dx.doi.org/10.1016/j.ceb.2013.08.005] [PMID: 24529241]

[6]
Li, J.; Li, Z.; Zheng, W.; Li, X.; Wang, Z.; Cui, Y.; Jiang, X. LncRNA-ATB: An indispensable cancer-related long noncoding RNA. Cell Prolif.,  2017, 50(6), e12381.
 [http://dx.doi.org/10.1111/cpr.12381] [PMID: 28884871]

[7]
Wu, Q.; Ma, J.; Meng, W.; Hui, P. DLX6-AS1 promotes cell proliferation, migration and EMT of gastric cancer through FUS-regulated MAP4K1. Cancer Biol. Ther.,  2020, 21(1), 17-25.
 [http://dx.doi.org/10.1080/15384047.2019.1647050] [PMID: 31591939]

[8]
Xin, Y.; Li, Z.; Shen, J.; Chan, M.T.; Wu, W.K. CCAT1: A pivotal oncogenic long non-coding RNA in human cancers. Cell Prolif.,  2016, 49(3), 255-260.
 [http://dx.doi.org/10.1111/cpr.12252] [PMID: 27134049]

[9]
Lu, T.X.; Rothenberg, M.E. MicroRNA. J. Allergy Clin. Immunol.,  2018, 141(4), 1202-1207.
 [http://dx.doi.org/10.1016/j.jaci.2017.08.034] [PMID: 29074454]

[10]
Ong, S.G.; Lee, W.H.; Kodo, K.; Wu, J.C. MicroRNA-mediated regulation of differentiation and trans-differentiation in stem cells. Adv. Drug Deliv. Rev.,  2015, 88, 3-15.
 [http://dx.doi.org/10.1016/j.addr.2015.04.004] [PMID: 25887992]

[11]
Liu, X.; Zhou, Y.; Ning, Y.E.; Gu, H.; Tong, Y.; Wang, N. MiR-195-5p inhibits malignant progression of cervical cancer by targeting YAP1. OncoTargets Ther.,  2020, 13, 931-944.
 [http://dx.doi.org/10.2147/OTT.S227826] [PMID: 32099397]

[12]
Zhang, X.; Wang, W.; Zhu, W.; Dong, J.; Cheng, Y.; Yin, Z.; Shen, F. Mechanisms and functions of long non-coding RNAs at multiple regulatory levels. Int. J. Mol. Sci.,  2019, 20(22), E5573.
 [http://dx.doi.org/10.3390/ijms20225573] [PMID: 31717266]

[13]
Liang, W.H.; Li, N.; Yuan, Z.Q.; Qian, X.L.; Wang, Z.H. DSCAM-AS1 promotes tumor growth of breast cancer by reducing miR-204-5p and up-regulating RRM2. Mol. Carcinog.,  2019, 58(4), 461-473.
 [http://dx.doi.org/10.1002/mc.22941] [PMID: 30457164]

[14]
Zhao, W.; Luo, J.; Jiao, S. Comprehensive characterization of cancer subtype associated long non-coding RNAs and their clinical implications. Sci. Rep.,  2014, 4, 6591.
 [http://dx.doi.org/10.1038/srep06591] [PMID: 25307233]

[15]
Qiu, Z.; Pan, X.X.; You, D.Y. LncRNA DSCAM-AS1 promotes non-small cell lung cancer progression via regulating miR-577/HMGB1 axis. Neoplasma,  2020, 67(4), 871-879.
 [http://dx.doi.org/10.4149/neo_2020_190826N821] [PMID: 32386483]

[16]
Liao, J.; Xie, N. Long noncoding RNA DSCAM-AS1 functions as an oncogene in non-small cell lung cancer by targeting BCL11A. Eur. Rev. Med. Pharmacol. Sci.,  2019, 23(3), 1087-1092.
 [PMID: 30779076]

[17]
Gao, L.; Chen, X.; Wang, Y.; Zhang, J. Up-regulation of FSTL3, regulated by lncRNA DSCAM-AS1/miR-122-5p axis, promotes proliferation and migration of non-small cell lung cancer cells. OncoTargets Ther.,  2020, 13, 2725-2738.
 [http://dx.doi.org/10.2147/OTT.S236359] [PMID: 32280246]

[18]
Liang, J.; Zhang, S.; Wang, W.; Xu, Y.; Kawuli, A.; Lu, J.; Xiu, X. Long non-coding RNA DSCAM-AS1 contributes to the tumorigenesis of cervical cancer by targeting miR-877-5p/ATXN7L3 axis. Biosci. Rep.,  2020, 40(1), BSR20192061.
 [http://dx.doi.org/10.1042/BSR20192061] [PMID: 31737900]

[19]
Ning, Y.; Bai, Z. DSCAM-AS1 accelerates cell proliferation and migration in osteosarcoma through miR-186-5p/GPRC5A signaling. Cancer Biomark.,  2021, 30(1), 29-39.
 [http://dx.doi.org/10.3233/CBM-190703] [PMID: 32865178]

[20]
DL Zhang, S.; Gao, F.; Fan, H. Long non-coding RNA DSCAM-AS1 upregulates USP47 expression through sponging miR-101-3p to accelerate osteosarcoma progression. Biochem. Cell Biol.,  2020, 98, 5.

[21]
Lu, C.; Xie, T.; Guo, X.; Wu, D.; Li, S.; Li, X.; Lu, Y.; Wang, X. LncRNA DSCAM-AS1 promotes colon cancer cells proliferation and migration via regulating the miR-204/SOX4 Axis. Cancer Manag. Res.,  2020, 12, 4347-4356.
 [http://dx.doi.org/10.2147/CMAR.S250670] [PMID: 32606930]

[22]
Li, B.; Sun, H.; Zhang, J. LncRNA DSCAM-AS1 promotes colorectal cancer progression by acting as a molecular sponge of miR-384 to modulate AKT3 expression. Aging (Albany NY),  2020, 12(10), 9781-9792.
 [http://dx.doi.org/10.18632/aging.103243] [PMID: 32453706]

[23]
Xu, J.; Wu, G.; Zhao, Y.; Han, Y.; Zhang, S.; Li, C.; Zhang, J. Long noncoding RNA DSCAM-AS1 facilitates colorectal cancer cell proliferation and migration via miR-137/Notch1 Axis. J. Cancer,  2020, 11(22), 6623-6632.
 [http://dx.doi.org/10.7150/jca.46562] [PMID: 33046983]

[24]
Ma, Y.; Bu, D.; Long, J.; Chai, W.; Dong, J. LncRNA DSCAM-AS1 acts as a sponge of miR-137 to enhance Tamoxifen resistance in breast cancer. J. Cell. Physiol.,  2019, 234(3), 2880-2894.
 [http://dx.doi.org/10.1002/jcp.27105] [PMID: 30203615]

[25]
Wang, N.; Yang, Y.; Jia, G.Z.; Wang, K.; Zhou, S.; Zhang, B.; Zhang, Z.S.; Qiao, Q.; He, X.L. Long non-coding RNA Down syndrome cell adhesion molecule-anti-sense 1 promotes gastric carcinoma cell proliferation and migration by regulating the miR-204/TPT1 axis. Hum. Exp. Toxicol.,  2021, 40(12)(Suppl.), S187-S195.
 [http://dx.doi.org/10.1177/09603271211036037] [PMID: 34372727]

[26]
Li, L.; Chen, P.; Huang, B.; Cai, P. lncRNA DSCAM-AS1 facilitates the progression of endometrial cancer via miR-136-5p. Oncol. Lett.,  2021, 22(6), 825.
 [http://dx.doi.org/10.3892/ol.2021.13086] [PMID: 34691252]

[27]
Thin, K.Z.; Liu, X.; Feng, X.; Raveendran, S.; Tu, J.C. LncRNA-DANCR: A valuable cancer related long non-coding RNA for human cancers. Pathol. Res. Pract.,  2018, 214(6), 801-805.
 [http://dx.doi.org/10.1016/j.prp.2018.04.003] [PMID: 29728310]

[28]
Das, S.; Ghosal, S.; Sen, R.; Chakrabarti, J. lnCeDB: Database of human long noncoding RNA acting as competing endogenous RNA. PLoS One,  2014, 9(6), e98965.
 [http://dx.doi.org/10.1371/journal.pone.0098965] [PMID: 24926662]

[29]
Ghafouri-Fard, S.; Khoshbakht, T.; Taheri, M.; Ebrahimzadeh, K. A review on the carcinogenic roles of DSCAM-AS1. Front. Cell Dev. Biol.,  2021, 9, 758513.
 [http://dx.doi.org/10.3389/fcell.2021.758513] [PMID: 34708048]

[30]
Matsui, M.; Corey, D.R. Non-coding RNAs as drug targets. Nat. Rev. Drug Discov.,  2017, 16(3), 167-179.
 [http://dx.doi.org/10.1038/nrd.2016.117] [PMID: 27444227]

[31]
Buskwofie, A.; David-West, G.; Clare, C.A. A review of cervical cancer: Incidence and disparities. J. Natl. Med. Assoc.,  2020, 112(2), 229-232.
 [http://dx.doi.org/10.1016/j.jnma.2020.03.002] [PMID: 32278478]

[32]
Hu, Z.; Ma, D. The precision prevention and therapy of HPV-related cervical cancer: New concepts and clinical implications. Cancer Med.,  2018, 7(10), 5217-5236.
 [http://dx.doi.org/10.1002/cam4.1501] [PMID: 30589505]

[33]
Seijo, L.M.; Peled, N.; Ajona, D.; Boeri, M.; Field, J.K.; Sozzi, G.; Pio, R.; Zulueta, J.J.; Spira, A.; Massion, P.P.; Mazzone, P.J.; Montuenga, L.M. Biomarkers in lung cancer screening: Achievements, promises, and challenges. J. Thorac. Oncol.,  2019, 14(3), 343-357.
 [http://dx.doi.org/10.1016/j.jtho.2018.11.023] [PMID: 30529598]

[34]
Łochowski, M.; Łochowska, B.; Rębowski, M.; Brzeziński, D.; Cieślik-Wolski, B.; Kozak, J. Five-year survival analysis and prognostic factors in patients operated on for non-small cell lung cancer with N2 disease. J. Thorac. Dis.,  2018, 10(6), 3180-3186.
 [http://dx.doi.org/10.21037/jtd.2018.05.173] [PMID: 30069313]

[35]
Zhang, W.; Shen, C.; Li, C.; Yang, G.; Liu, H.; Chen, X.; Zhu, D.; Zou, H.; Zhen, Y.; Zhang, D.; Zhao, S. miR-577 inhibits glioblastoma tumor growth via the Wnt signaling pathway. Mol. Carcinog.,  2016, 55(5), 575-585.
 [http://dx.doi.org/10.1002/mc.22304] [PMID: 25764520]

[36]
Wang, W.; Smits, R.; Hao, H.; He, C. Wnt/β-catenin signaling in liver cancers. Cancers (Basel),  2019, 11(7), E926.
 [http://dx.doi.org/10.3390/cancers11070926] [PMID: 31269694]

[37]
Yu, Y.; Wang, J.; Khaled, W.; Burke, S.; Li, P.; Chen, X.; Yang, W.; Jenkins, N.A.; Copeland, N.G.; Zhang, S.; Liu, P. Bcl11a is essential for lymphoid development and negatively regulates p53. J. Exp. Med.,  2012, 209(13), 2467-2483.
 [http://dx.doi.org/10.1084/jem.20121846] [PMID: 23230003]

[38]
Qin, H.; Sha, J.; Jiang, C.; Gao, X.; Qu, L.; Yan, H.; Xu, T.; Jiang, Q.; Gao, H. miR-122 inhibits metastasis and epithelial-mesenchymal transition of non-small-cell lung cancer cells. OncoTargets Ther.,  2015, 8, 3175-3184.
 [PMID: 26604787]

[39]
Ni, X.; Cao, X.; Wu, Y.; Wu, J. FSTL1 suppresses tumor cell proliferation, invasion and survival in non-small cell lung cancer. Oncol. Rep.,  2018, 39(1), 13-20.
 [PMID: 29115636]

[40]
Cersosimo, F.; Lonardi, S.; Bernardini, G.; Telfer, B.; Mandelli, G.E.; Santucci, A.; Vermi, W.; Giurisato, E. Tumor-associated macrophages in osteosarcoma: From mechanisms to therapy. Int. J. Mol. Sci.,  2020, 21(15), E5207.
 [http://dx.doi.org/10.3390/ijms21155207] [PMID: 32717819]

[41]
Harrison, D.J.; Geller, D.S.; Gill, J.D.; Lewis, V.O.; Gorlick, R. Current and future therapeutic approaches for osteosarcoma. Expert Rev. Anticancer Ther.,  2018, 18(1), 39-50.
 [http://dx.doi.org/10.1080/14737140.2018.1413939] [PMID: 29210294]

[42]
Huang, H.; Yang, X.; Chen, J.; Fu, J.; Chen, C.; Wen, J.; Mo, Q. lncRNA DGCR5 inhibits the proliferation of colorectal cancer cells by downregulating miR-21. Oncol. Lett.,  2019, 18(3), 3331-3336.
 [http://dx.doi.org/10.3892/ol.2019.10671] [PMID: 31452812]

[43]
Lan, G.; Lin, Z.; Zhang, J.; Liu, L.; Zhang, J.; Zheng, L.; Luo, Q. Notch pathway is involved in the suppression of colorectal cancer by embryonic stem cell microenvironment. OncoTargets Ther.,  2019, 12, 2869-2878.
 [http://dx.doi.org/10.2147/OTT.S199046] [PMID: 31114232]

[44]
Sung, H.; Ferlay, J.; Siegel, R.L.; Laversanne, M.; Soerjomataram, I.; Jemal, A.; Bray, F. Global cancer statistics 2020: Globocan estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J. Clin.,  2021, 71(3), 209-249.
 [http://dx.doi.org/10.3322/caac.21660] [PMID: 33538338]

[45]
Niknafs, Y.S.; Han, S.; Ma, T.; Speers, C.; Zhang, C.; Wilder-Romans, K.; Iyer, M.K.; Pitchiaya, S.; Malik, R.; Hosono, Y.; Prensner, J.R.; Poliakov, A.; Singhal, U.; Xiao, L.; Kregel, S.; Siebenaler, R.F.; Zhao, S.G.; Uhl, M.; Gawronski, A.; Hayes, D.F.; Pierce, L.J.; Cao, X.; Collins, C.; Backofen, R.; Sahinalp, C.S.; Rae, J.M.; Chinnaiyan, A.M.; Feng, F.Y. The lncRNA landscape of breast cancer reveals a role for DSCAM-AS1 in breast cancer progression. Nat. Commun.,  2016, 7, 12791.
 [http://dx.doi.org/10.1038/ncomms12791] [PMID: 27666543]

[46]
Haque, R.; Ahmed, S.A.; Inzhakova, G.; Shi, J.; Avila, C.; Polikoff, J.; Bernstein, L.; Enger, S.M.; Press, M.F. Impact of breast cancer subtypes and treatment on survival: An analysis spanning two decades. Cancer Epidemiol. Biomarkers Prev.,  2012, 21(10), 1848-1855.
 [http://dx.doi.org/10.1158/1055-9965.EPI-12-0474] [PMID: 22989461]

[47]
Shah, K.N.; Wilson, E.A.; Malla, R.; Elford, H.L.; Faridi, J.S. Targeting ribonucleotide reductase M2 and NF-κB activation with didox to circumvent tamoxifen resistance in breast cancer. Mol. Cancer Ther.,  2015, 14(11), 2411-2421.
 [http://dx.doi.org/10.1158/1535-7163.MCT-14-0689] [PMID: 26333382]

[48]
Smyth, E.C.; Nilsson, M.; Grabsch, H.I.; van Grieken, N.C.; Lordick, F. Gastric cancer. Lancet,  2020, 396(10251), 635-648.
 [http://dx.doi.org/10.1016/S0140-6736(20)31288-5] [PMID: 32861308]

[49]
Matsuoka, T.; Yashiro, M. Biomarkers of gastric cancer: Current topics and future perspective. World J. Gastroenterol.,  2018, 24(26), 2818-2832.
 [http://dx.doi.org/10.3748/wjg.v24.i26.2818] [PMID: 30018477]

[50]
Sideris, M.; Emin, E.I.; Abdullah, Z.; Hanrahan, J.; Stefatou, K.M.; Sevas, V.; Emin, E.; Hollingworth, T.; Odejinmi, F.; Papagrigoriadis, S.; Vimplis, S.; Willmott, F. The role of KRAS in endometrial cancer: A mini-review. Anticancer Res.,  2019, 39(2), 533-539.
 [http://dx.doi.org/10.21873/anticanres.13145] [PMID: 30711927]

[51]
Aoki, Y.; Kanao, H.; Wang, X.; Yunokawa, M.; Omatsu, K.; Fusegi, A.; Takeshima, N. Adjuvant treatment of endometrial cancer today. Jpn. J. Clin. Oncol.,  2020, 50(7), 753-765.
 [http://dx.doi.org/10.1093/jjco/hyaa071] [PMID: 32463094]

Cite As

Mini-Reviews in Medicinal Chemistry

LncRNA DSCAM-AS1: A Pivotal Therapeutic Target in Cancer

Abstract

Graphical Abstract