Full Text:   <2157>

Summary:  <1424>

CLC number: Q39

On-line Access: 2019-01-07

Received: 2018-04-27

Revision Accepted: 2018-09-16

Crosschecked: 2018-12-05

Cited: 0

Clicked: 3230

Citations:  Bibtex RefMan EndNote GB/T7714


Ai-fu Lin


-   Go to

Article info.
Open peer comments

Journal of Zhejiang University SCIENCE B 2019 Vol.20 No.1 P.1-8


Role of cytoplasmic lncRNAs in regulating cancer signaling pathways

Author(s):  Pei-fen Fu, Xin Zheng, Xiao Fan, Ai-fu Lin

Affiliation(s):  The Breast Centre, the First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, China; more

Corresponding email(s):   fupeifen@hotmail.com, linaifu@zju.edu.cn

Key Words:  Long noncoding RNA (lncRNA), Cancer signaling, Cancer therapy, Biomarker

Share this article to: More |Next Article >>>

Pei-fen Fu, Xin Zheng, Xiao Fan, Ai-fu Lin. Role of cytoplasmic lncRNAs in regulating cancer signaling pathways[J]. Journal of Zhejiang University Science B, 2019, 20(1): 1-8.

@article{title="Role of cytoplasmic lncRNAs in regulating cancer signaling pathways",
author="Pei-fen Fu, Xin Zheng, Xiao Fan, Ai-fu Lin",
journal="Journal of Zhejiang University Science B",
publisher="Zhejiang University Press & Springer",

%0 Journal Article
%T Role of cytoplasmic lncRNAs in regulating cancer signaling pathways
%A Pei-fen Fu
%A Xin Zheng
%A Xiao Fan
%A Ai-fu Lin
%J Journal of Zhejiang University SCIENCE B
%V 20
%N 1
%P 1-8
%@ 1673-1581
%D 2019
%I Zhejiang University Press & Springer
%DOI 10.1631/jzus.B1800254

T1 - Role of cytoplasmic lncRNAs in regulating cancer signaling pathways
A1 - Pei-fen Fu
A1 - Xin Zheng
A1 - Xiao Fan
A1 - Ai-fu Lin
J0 - Journal of Zhejiang University Science B
VL - 20
IS - 1
SP - 1
EP - 8
%@ 1673-1581
Y1 - 2019
PB - Zhejiang University Press & Springer
ER -
DOI - 10.1631/jzus.B1800254

Cancer remains a serious healthcare problem despite significant improvements in early detection and treatment approaches in the past few decades. Novel biomarkers for diagnosis and therapeutic strategies are urgently needed. In recent years, long noncoding RNAs (lncRNAs) have been reported to be aberrantly expressed in tumors and show crosstalk with key cancer-related signaling pathways. In this review, we summarized the current progress of research on cytoplasmic lncRNAs and their roles in regulating cancer signaling and tumor progression, further characterization of which may lead to effective approaches for cancer prevention and therapy.



Darkslateblue:Affiliate; Royal Blue:Author; Turquoise:Article


[1]Altomare DA, Testa JR, 2005. Perturbations of the AKT signaling pathway in human cancer. Oncogene, 24(50):7455-7464.

[2]Angers S, Moon RT, 2009. Proximal events in Wnt signal transduction. Nat Rev Mol Cell Biol, 10(7):468-477.

[3]Atala A, 2014. Re: lncRNA-dependent mechanisms of androgen-receptor-regulated gene activation programs. J Urol, 191(5):1470-1471.

[4]Batista PJ, Chang HY, 2013. Long noncoding RNAs: cellular address codes in development and disease. Cell, 152(6):1298-1307.

[5]Beyer TA, Weiss A, Khomchuk Y, et al., 2013. Switch enhancers interpret TGF-β and Hippo signaling to control cell fate in human embryonic stem cells. Cell Rep, 5(6):1611-1624.

[6]Cheetham SW, Gruhl F, Mattick JS, et al., 2013. Long noncoding RNAs and the genetics of cancer. Br J Cancer, 108(12):2419-2425.

[7]Chen DH, Sun YT, Wei YK, et al., 2012. LIFR is a breast cancer metastasis suppressor upstream of the Hippo-YAP pathway and a prognostic marker. Nat Med, 18(10):1511-1517.

[8]Chen Q, Zhang NL, Gray RS, et al., 2014. A temporal requirement for Hippo signaling in mammary gland differentiation, growth, and tumorigenesis. Genes Dev, 28(5):432-437.

[9]Citri A, Yarden Y, 2006. EGF-ERBB signalling: towards the systems level. Nat Rev Mol Cell Biol, 7(7):505-516.

[10]Cordenonsi M, Zanconato F, Azzolin L, et al., 2011. The Hippo transducer TAZ confers cancer stem cell-related traits on breast cancer cells. Cell, 147(4):759-772.

[11]Denko NC, 2008. Hypoxia, HIF1 and glucose metabolism in the solid tumour. Nat Rev Cancer, 8(9):705-713.

[12]Dong JX, Feldmann G, Huang JB, et al., 2007. Elucidation of a universal size-control mechanism in Drosophila and mammals. Cell, 130(6):1120-1133.

[13]Gibb EA, Brown CJ, Lam WL, 2011. The functional role of long non-coding RNA in human carcinomas. Mol Cancer, 10:38.

[14]Guo YZ, Sun HH, Wang XT, et al., 2018. Transcriptomic analysis reveals key lncRNAs associated with ribosomal biogenesis and epidermis differentiation in head and neck squamous cell carcinoma. J Zhejiang Univ-Sci B (Biomed & Biotechnol), 19(9):674-688.

[15]Gutschner T, Diederichs S, 2012. The hallmarks of cancer: a long non-coding RNA point of view. RNA Biol, 9(6):703-719.

[16]Hadji F, Boulanger MC, Guay SP, et al., 2016. Altered DNA methylation of long noncoding RNA H19 in calcific aortic valve disease promotes mineralization by silencing NOTCH1. Circulation, 134(23):1848-1862.

[17]Halder G, Johnson RL, 2011. Hippo signaling: growth control and beyond. Development, 138(1):9-22.

[18]Harvey KF, Zhang XM, Thomas DM, 2013. The Hippo pathway and human cancer. Nat Rev Cancer, 13(4):246-257.

[19]Haskins JW, Nguyen DX, Stern DF, 2014. Neuregulin 1-activated ERBB4 interacts with YAP to induce Hippo pathway target genes and promote cell migration. Sci Signal, 7(355):ra116.

[20]Hirai H, Sootome H, Nakatsuru Y, et al., 2010. MK-2206, an allosteric Akt inhibitor, enhances antitumor efficacy by standard chemotherapeutic agents or molecular targeted drugs in vitro and in vivo. Mol Cancer Ther, 9(7):1956-1967.

[21]Jiang MH, Zhang SK, Yang ZH, et al., 2018. Self-recognition of an inducible host lncRNA by RIG-I feedback restricts innate immune response. Cell, 173(4):906-919.e13.

[22]Kaelin WG Jr, Ratcliffe PJ, 2008. Oxygen sensing by metazoans: the central role of the HIF hydroxylase pathway. Mol Cell, 30(4):393-402.

[23]Keith B, Johnson RS, Simon MC, 2011. HIF1α and HIF2α: sibling rivalry in hypoxic tumour growth and progression. Nat Rev Cancer, 12(1):9-22.

[24]Kuschel A, Simon P, Tug S, 2012. Functional regulation of HIF-1α under normoxia—is there more than post-translational regulation? J Cell Physiol, 227(2):514-524.

[25]Li CL, Wang SY, Xing Z, et al., 2017. A ROR1-HER3-lncRNA signalling axis modulates the Hippo-YAP pathway to regulate bone metastasis. Nat Cell Biol, 19(2):106-119.

[26]Lian I, Kim J, Okazawa H, et al., 2010. The role of YAP transcription coactivator in regulating stem cell self-renewal and differentiation. Genes Dev, 24(11):1106-1118.

[27]Lin AF, Piao HL, Zhuang L, et al., 2014a. FoxO transcription factors promote AKT Ser473 phosphorylation and renal tumor growth in response to pharmacologic inhibition of the PI3K-AKT pathway. Cancer Res, 74(6):1682-1693.

[28]Lin AF, Yao J, Zhuang L, et al., 2014b. The FoxO-BNIP3 axis exerts a unique regulation of mTORC1 and cell survival under energy stress. Oncogene, 33(24):3183-3194.

[29]Lin AF, Li CL, Xing Z, et al., 2016. The LINK-A lncRNA activates normoxic HIF1α signalling in triple-negative breast cancer. Nat Cell Biol, 18(2):213-224.

[30]Lin AF, Hu QS, Li CL, et al., 2017. The LINK-A lncRNA interacts with PtdIns(3,4,5)P3 to hyperactivate AKT and confer resistance to AKT inhibitors. Nat Cell Biol, 19(3):238-251.

[31]Ling H, Spizzo R, Atlasi Y, et al., 2013. Ccat2, a novel noncoding RNA mapping to 8q24, underlies metastatic progression and chromosomal instability in colon cancer. Genome Res, 23(9):1446-1461.

[32]Liu BD, Sun LJ, Liu Q, et al., 2015. A cytoplasmic NF-κB interacting long noncoding RNA blocks IκB phosphorylation and suppresses breast cancer metastasis. Cancer Cell, 27(3):370-381.

[33]Luo J, Manning BD, Cantley LC, 2003. Targeting the PI3K-Akt pathway in human cancer: rationale and promise. Cancer Cell, 4(4):257-262.

[34]Ma YX, Zhang JM, Wen LX, et al., 2018. Membrane-lipid associated lncRNA: a new regulator in cancer signaling. Cancer Lett, 419:27-29.

[35]Manning BD, Cantley LC, 2007. AKT/PKB signaling: navigating downstream. Cell, 129(7):1261-1274.

[36]Mayer IA, Arteaga CL, 2016. The PI3K/AKT pathway as a target for cancer treatment. Ann Rev Med, 67:11-28.

[37]Miah S, Martin A, Lukong KE, 2012. Constitutive activation of breast tumor kinase accelerates cell migration and tumor growth in vivo. Oncogenesis, 1:e11.

[38]Ntziachristos P, Lim JS, Sage J, et al., 2014. From fly wings to targeted cancer therapies: a centennial for notch signaling. Cancer Cell, 25(3):318-334.

[39]Overholtzer M, Zhang JM, Smolen GA, et al., 2006. Transforming properties of YAP, a candidate oncogene on the chromosome 11q22 amplicon. Proc Natl Acad Sci USA, 103(33):12405-12410.

[40]Pan DJ, 2010. The Hippo signaling pathway in development and cancer. Dev Cell, 19(4):491-505.

[41]Pawson T, Warner N, 2007. Oncogenic re-wiring of cellular signaling pathways. Oncogene, 26(9):1268-1275.

[42]Ponting CP, Oliver PL, Reik W, 2009. Evolution and functions of long noncoding RNAs. Cell, 136(4):629-641.

[43]Prensner JR, Chinnaiyan AM, 2011. The emergence of lncRNAs in cancer biology. Cancer Discov, 1(5):391-407.

[44]Salah Z, Itzhaki E, Aqeilan RI, 2014. The ubiquitin E3 ligase ITCH enhances breast tumor progression by inhibiting the Hippo tumor suppressor pathway. Oncotarget, 5(21):10886-10900.


[46]Sang LJ, Ju HQ, Liu GP, et al., 2018. LncRNA Camk-A regulates Ca2+-signaling-mediated tumor microenvironment remodeling. Mol Cell, 72(1):71-83.e7.

[47]Schwab LP, Peacock DL, Majumdar D, et al., 2012. Hypoxia-inducible factor 1α promotes primary tumor growth and tumor-initiating cell activity in breast cancer. Breast Cancer Res, 14(1):R6.

[48]Song QH, Mao BB, Cheng JB, et al., 2015. YAP enhances autophagic flux to promote breast cancer cell survival in response to nutrient deprivation. PLoS ONE, 10(3):e0120790.

[49]Talks KL, Turley H, Gatter KC, et al., 2000. The expression and distribution of the hypoxia-inducible factors HIF-1α and HIF-2α in normal human tissues, cancers, and tumor-associated macrophages. Am J Pathol, 157(2):411-421.

[50]Tano K, Akimitsu N, 2012. Long non-coding RNAs in cancer progression. Front Genet, 3:219.

[51]Vivanco I, Sawyers CL, 2002. The phosphatidylinositol 3-kinase-AKT pathway in human cancer. Nat Rev Cancer, 2(7):489-501.

[52]Wang P, Xue YQ, Han YM, et al., 2014. The STAT3-binding long noncoding RNA lnc-DC controls human dendritic cell differentiation. Science, 344(6181):310-313.

[53]Wang P, Xu JF, Wang YJ, et al., 2017. An interferon-independent lncRNA promotes viral replication by modulating cellular metabolism. Science, 358(6366):1051-1055.

[54]Wang WQ, Huang J, Chen JJ, 2011. Angiomotin-like proteins associate with and negatively regulate YAP1. J Biol Chem, 286(6):4364-4370.

[55]Wang WQ, Huang J, Wang X, et al., 2012. PTPN14 is required for the density-dependent control of YAP1. Genes Dev, 26(17):1959-1971.

[56]Wang YY, He L, Du Y, et al., 2015. The long noncoding RNA lncTCF7 promotes self-renewal of human liver cancer stem cells through activation of Wnt signaling. Cell Stem Cell, 16(4):413-425.

[57]Wapinski O, Chang HY, 2011. Long noncoding RNAs and human disease. Trends Cell Biol, 21(6):354-361.

[58]Xing Z, Lin AF, Li CL, et al., 2014. lncRNA directs cooperative epigenetic regulation downstream of chemokine signals. Cell, 159(5):1110-1125.

[59]Yan K, Tian J, Shi W, et al., 2017. LncRNA SNHG6 is associated with poor prognosis of gastric cancer and promotes cell proliferation and EMT through epigenetically silencing p27 and sponging miR-101-3p. Cell Physiol Biochem, 42(3):999-1012.

[60]Yang GD, Lu XZ, Yuan LJ, 2014. LncRNA: a link between RNA and cancer. Biochim Biophys Acta, 1839(11):1097-1109.

[61]Yu FX, Zhao B, Guan KL, 2015. Hippo pathway in organ size control, tissue homeostasis, and cancer. Cell, 163(4):811-828.

[62]Zhao B, Li L, Lei QY, et al., 2010. The Hippo-YAP pathway in organ size control and tumorigenesis: an updated version. Genes Dev, 24(9):862-874.

[63]Zheng X, Han H, Liu GP, et al., 2017. LncRNA wires up Hippo and hedgehog signaling to reprogramme glucose metabolism. EMBO J, 36(22):3325-3335.


[65]Zhong H, de Marzo AM, Laughner E, et al., 1999. Overexpression of hypoxia-inducible factor 1α in common human cancers and their metastases. Cancer Res, 59(22):5830-5835.

[66]Zhou X, Wang SY, Wang Z, et al., 2015. Estrogen regulates Hippo signaling via GPER in breast cancer. J Clin Invest, 125(5):2123-2135.

Open peer comments: Debate/Discuss/Question/Opinion


Please provide your name, email address and a comment

Journal of Zhejiang University-SCIENCE, 38 Zheda Road, Hangzhou 310027, China
Tel: +86-571-87952783; E-mail: cjzhang@zju.edu.cn
Copyright © 2000 - 2024 Journal of Zhejiang University-SCIENCE