Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

Keynote webinar | Spotlight on medication adherence

LIVE: Thursday 27th June 2024, 18:00-19:30 (CEST)
Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.
ADVANCED SEARCH
Log in
Top
Cancer Cell International
Published in: Cancer Cell International 1/2020

Open Access 01-12-2020 | Prostate Cancer | Primary research

LncRNA LEF1-AS1 promotes metastasis of prostatic carcinoma via the Wnt/β-catenin pathway

Authors: Weiyuan Li, Ganggang Yang, Dengke Yang, Dong Li, Qian Sun

Published in: Cancer Cell International | Issue 1/2020

Login to get access

Abstract

Background

Long noncoding RNAs (lncRNAs) are important functional regulators of many biological processes of cancers. However, the mechanisms by which lncRNAs modulate androgen-independent prostate cancer (AIPC) development remain largely unknown.

Methods

Next-generation sequencing technology and RT-qPCR were used to assess LEF1-AS1 expression level in AIPC tissues and adjacent normal tissues. Functional in vitro experiments, including colony formation, EDU and transwell assays were performed to assess the role of LEF1-AS1 in AIPC. Xenograft assays were conducted to assess the effect of LEF1-AS1 on cell proliferation in vivo. Chromatin immunoprecipitation (ChIP) and RNA binding protein immunoprecipitation (RIP) assays were performed to elucidate the regulatory network of LEF1-AS1.

Results

The next-generation sequencing results showed that LEF1-AS1 is significantly overexpressed in AIPC. Furthermore, our RT-qPCR assay data showed that LEF1-AS1 is overexpressed in AIPC tissues. Functional experiments showed that LEF1-AS1 promotes the proliferation, migration, invasion and angiogenic ability of AIPC cells in vitro and tumour growth in vivo by recruiting the transcription factor C-myb to the promoter of FZD2, inducing its transcription. Furthermore, LEF1-AS1 was shown to function as a competing endogenous RNA (ceRNA) that sponges miR-328 to activate CD44.

Conclusion

In summary, the results of our present study revealed that LEF1-AS1 acts as a tumour promoter in the progression of AIPC. Furthermore, the results revealed that LEF1-AS1 functions as a ceRNA and regulates Wnt/β-catenin pathway activity via FZD2 and CD44. Our results provide new insights into the mechanism that links the function of LEF1-AS1 with AIPC and suggests that LEF1-AS1 may serve as a novel potential target for the improvement of AIPC therapy.
Appendix
Available only for authorised users
Literature
1.
Siegel R, Naishadham D, Jemal A. Cancer statistics, 2013. CA Cancer J Clin. 2013;63(1):11–30.CrossRef
2.
Heidenreich A, Aus G, Bolla M, Joniau S, Matveev VB, Schmid HP, Zattoni F. EAU guidelines on prostate cancer. Eur Urol. 2008;53(1):68–80.CrossRef
3.
Klein EA, Silverman R. Inflammation, infection, and prostate cancer. Curr Opin Urol. 2008;18(3):315–9.CrossRef
4.
Ponting CP, Oliver PL, Reik W. Evolution and functions of long noncoding RNAs. Cell. 2009;136(4):629–41.CrossRef
5.
Seton-Rogers S. Non-coding RNAs: The cancer X factor. Nat Rev Cancer. 2013;13(4):224–5.CrossRef
6.
Schmitt AM, Chang HY. Long noncoding RNAs in cancer pathways. Cancer Cell. 2016;29(4):452–63.CrossRef
7.
Lin D: Commentary on "The oestrogen receptor alpha-regulated lncRNA NEAT1 is a critical modulator of prostate cancer." Chakravarty D, Sboner A, Nair SS, Giannopoulou E, Li R, Hennig S, Mosquera JM, Pauwels J, Park K, Kossai M, MacDonald TY, Fontugne J, Erho N, Vergara IA, Ghadessi M, Davicioni E, Jenkins RB, Palanisamy N, Chen Z, Nakagawa S, Hirose T, Bander NH, Beltran H, Fox AH, Elemento O, Rubin MA, University of Washington-Urology, Seattle, WA. Nat Commun 2014; 5:5383. Urologic oncology 2016, 34(11):522.
8.
Fagerberg L, Hallström BM, Oksvold P, Kampf C, Djureinovic D, Odeberg J, Habuka M, Tahmasebpoor S, Danielsson A, Edlund K, et al. Analysis of the human tissue-specific expression by genome-wide integration of transcriptomics and antibody-based proteomics. Mol Cell Proteomics. 2014;13(2):397–406.CrossRef
9.
Wang J, Liu X, Yan C, Liu J, Wang S, Hong Y, Gu A, Zhao P. LEF1-AS1, a long-noncoding RNA, promotes malignancy in glioblastoma. OncoTargets Ther. 2017;10:4251–60.CrossRef
10.
Sun T, Liu Z, Zhang R, Ma S, Lin T, Li Y, Yang S, Zhang W, Wang Y. Long Non-Coding RNA LEF1-AS1 Promotes Migration, Invasion and Metastasis of Colon Cancer Cells Through miR-30-5p/SOX9 Axis. OncoTargets Ther. 2020;13:2957–72.CrossRef
11.
Wang A, Zhao C, Gao Y. LEF1-AS1 contributes to proliferation and invasion through regulating miR-544a/ FOXP1 axis in lung cancer. Investig New Drugs. 2019;37(6):1127–34.CrossRef
12.
Nusse R, Clevers H. Wnt/β-catenin signaling, disease, and emerging therapeutic modalities. Cell. 2017;169(6):985–99.CrossRef
13.
Polakis P. The many ways of Wnt in cancer. Curr Opin Genet Dev. 2007;17(1):45–51.CrossRef
14.
Arend RC, Londoño-Joshi AI, Straughn JM Jr, Buchsbaum DJ. The Wnt/β-catenin pathway in ovarian cancer: a review. Gynecol Oncol. 2013;131(3):772–9.CrossRef
15.
Clevers H, Nusse R. Wnt/β-catenin signaling and disease. Cell. 2012;149(6):1192–205.CrossRef
16.
MacDonald BT, Tamai K, He X. Wnt/beta-catenin signaling: components, mechanisms, and diseases. Dev Cell. 2009;17(1):9–26.CrossRef
17.
Yu X, Wang Y, Jiang M, Bierie B, Roy-Burman P, Shen MM, Taketo MM, Wills M, Matusik RJ. Activation of beta-Catenin in mouse prostate causes HGPIN and continuous prostate growth after castration. Prostate. 2009;69(3):249–62.CrossRef
18.
Castellone MD, Teramoto H, Williams BO, Druey KM, Gutkind JS. Prostaglandin E2 promotes colon cancer cell growth through a Gs-axin-beta-catenin signaling axis. Science. 2005;310(5753):1504–10.CrossRef
19.
Lamberti C, Lin KM, Yamamoto Y, Verma U, Verma IM, Byers S, Gaynor RB. Regulation of beta-catenin function by the IkappaB kinases. J Biol Chem. 2001;276(45):42276–86.CrossRef
20.
Persad S, Troussard AA, McPhee TR, Mulholland DJ, Dedhar S. Tumor suppressor PTEN inhibits nuclear accumulation of beta-catenin and T cell/lymphoid enhancer factor 1-mediated transcriptional activation. J Cell Biol. 2001;153(6):1161–74.CrossRef
21.
Scher HI, Solo K, Valant J, Todd MB, Mehra M. Prevalence of prostate cancer clinical states and mortality in the United States: estimates using a dynamic progression model. PLoS ONE. 2015;10(10):e0139440.CrossRef
22.
Ferlay J, Soerjomataram I, Dikshit R, Eser S, Mathers C, Rebelo M, Parkin DM, Forman D, Bray F. Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer. 2015;136(5):E359-386.CrossRef
23.
de Oliveira JC, Oliveira LC, Mathias C, Pedroso GA, Lemos DS, Salviano-Silva A, Jucoski TS, Lobo-Alves SC, Zambalde EP, Cipolla GA, et al. Long non-coding RNAs in cancer: another layer of complexity. J Gene Med. 2019;21(1):e3065.PubMed
24.
Xiang C, Zhang Y, Zhang Y, Liu C, Hou Y, Zhang Y. lncRNA LEF1-AS1 promotes proliferation and induces apoptosis of non-small-cell lung cancer cells by regulating miR-221/PTEN signaling. Cancer Manage Res. 2020;12:3845–50.CrossRef
25.
Zhang C, Bao C, Zhang X, Lin X, Pan D, Chen Y. Knockdown of lncRNA LEF1-AS1 inhibited the progression of oral squamous cell carcinoma (OSCC) via Hippo signaling pathway. Cancer Biol Ther. 2019;20(9):1213–22.CrossRef
26.
Zhang Y, Ruan F. LncRNA LEF1-AS1 Promotes ovarian cancer development through interacting with miR-1285-3p. Cancer Manage Res. 2020;12:687–94.CrossRef
27.
Niehrs C, Acebron SP. Mitotic and mitogenic Wnt signalling. EMBO J. 2012;31(12):2705–13.CrossRef
28.
van Amerongen R, Nusse R. Towards an integrated view of Wnt signaling in development. Development. 2009;136(19):3205–14.CrossRef
29.
Merle P, Kim M, Herrmann M, Gupte A, Lefrançois L, Califano S, Trépo C, Tanaka S, Vitvitski L, de la Monte S, et al. Oncogenic role of the frizzled-7/beta-catenin pathway in hepatocellular carcinoma. J Hepatol. 2005;43(5):854–62.CrossRef
30.
Kim M, Lee HC, Tsedensodnom O, Hartley R, Lim YS, Yu E, Merle P, Wands JR. Functional interaction between Wnt3 and Frizzled-7 leads to activation of the Wnt/beta-catenin signaling pathway in hepatocellular carcinoma cells. J Hepatol. 2008;48(5):780–91.CrossRef
31.
Chen C, Zhao S, Karnad A, Freeman JW. The biology and role of CD44 in cancer progression: therapeutic implications. J Hematol Oncol. 2018;11(1):64.CrossRef
32.
Chang G, Zhang H, Wang J, Zhang Y, Xu H, Wang C, Zhang H, Ma L, Li Q, Pang T. CD44 targets Wnt/β-catenin pathway to mediate the proliferation of K562 cells. Cancer Cell Int. 2013;13(1):117.CrossRef
33.
Schmitt M, Metzger M, Gradl D, Davidson G, Orian-Rousseau V. CD44 functions in Wnt signaling by regulating LRP6 localization and activation. Cell Death Differ. 2015;22(4):677–89.CrossRef
Metadata
Title
LncRNA LEF1-AS1 promotes metastasis of prostatic carcinoma via the Wnt/β-catenin pathway
Authors
Weiyuan Li
Ganggang Yang
Dengke Yang
Dong Li
Qian Sun
Publication date
01-12-2020
Publisher
BioMed Central
Published in
Cancer Cell International / Issue 1/2020
Electronic ISSN: 1475-2867
DOI
https://doi.org/10.1186/s12935-020-01624-x

Other articles of this Issue 1/2020

Cancer Cell International 1/2020 Go to the issue

Review

Autophagy regulation using luteolin: new insight into its anti-tumor activity

Primary research

CircZDHHC20 represses the proliferation, migration and invasion in trophoblast cells by miR-144/GRHL2 axis

Primary research

Long non-coding RNA KCNQ1OT1 up-regulates CTNND1 by sponging miR-329-3p to induce the proliferation, migration, invasion, and inhibit apoptosis of colorectal cancer cells

Primary research

The Ibr-7 derivative of ibrutinib radiosensitizes pancreatic cancer cells by downregulating p-EGFR

Primary research

Enhanced expression of microtubule-associated protein 7 functioned as a contributor to cervical cancer cell migration and is predictive of adverse prognosis

Primary research

Circ_0000140 restrains the proliferation, metastasis and glycolysis metabolism of oral squamous cell carcinoma through upregulating CDC73 via sponging miR-182-5p
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine
Image Credits