Full Text:  <179>

Summary:  <4>

CLC number: 

On-line Access: 2024-04-07

Received: 2023-07-10

Revision Accepted: 2023-12-11

Crosschecked: 2024-04-07

Cited: 0

Clicked: 184

Citations:  Bibtex RefMan EndNote GB/T7714


Ai-fu Lin


-   Go to

Article info.
Open peer comments

Journal of Zhejiang University SCIENCE B

Accepted manuscript available online (unedited version)

Emerging role of lncRNAs as mechanical signaling molecules in mechanotransduction and their association with Hippo-YAP signaling: a review

Author(s):  Siyi LIN, Xinyu HE, Ying WANG, Yu CHEN, Aifu LIN

Affiliation(s):  College of Medicine, Zhejiang University, Hangzhou 310058, China; more

Corresponding email(s):  linaifu@zju.edu.cn

Key Words:  YAP/TAZ; Long non-coding RNA (lncRNA); Mechanotransduction; F-actin

Share this article to: More <<< Previous Paper|Next Paper >>>

Siyi LIN, Xinyu HE, Ying WANG, Yu CHEN, Aifu LIN. Emerging role of lncRNAs as mechanical signaling molecules in mechanotransduction and their association with Hippo-YAP signaling: a review[J]. Journal of Zhejiang University Science B,in press.Frontiers of Information Technology & Electronic Engineering,in press.https://doi.org/10.1631/jzus.B2300497

@article{title="Emerging role of lncRNAs as mechanical signaling molecules in mechanotransduction and their association with Hippo-YAP signaling: a review",
author="Siyi LIN, Xinyu HE, Ying WANG, Yu CHEN, Aifu LIN",
journal="Journal of Zhejiang University Science B",
year="in press",
publisher="Zhejiang University Press & Springer",

%0 Journal Article
%T Emerging role of lncRNAs as mechanical signaling molecules in mechanotransduction and their association with Hippo-YAP signaling: a review
%A Siyi LIN
%A Xinyu HE
%A Ying WANG
%A Aifu LIN
%J Journal of Zhejiang University SCIENCE B
%P 280-292
%@ 1673-1581
%D in press
%I Zhejiang University Press & Springer

T1 - Emerging role of lncRNAs as mechanical signaling molecules in mechanotransduction and their association with Hippo-YAP signaling: a review
A1 - Siyi LIN
A1 - Xinyu HE
A1 - Ying WANG
A1 - Yu CHEN
A1 - Aifu LIN
J0 - Journal of Zhejiang University Science B
SP - 280
EP - 292
%@ 1673-1581
Y1 - in press
PB - Zhejiang University Press & Springer
ER -

Cells within tissues are subject to various mechanical forces, including hydrostatic pressure, shear stress, compression, and tension. These mechanical stimuli can be converted into biochemical signals through mechanoreceptors or cytoskeleton-dependent response processes, shaping the microenvironment and maintaining cellular physiological balance. Several studies have demonstrated the roles of Yes-associated protein (YAP) and its homolog transcriptional coactivator with PDZ-binding motif (TAZ) as mechanotransducers, exerting dynamic influence on cellular phenotypes including differentiation and disease pathogenesis. This regulatory function entails the involvement of the cytoskeleton, nucleoskeleton, integrin, focal adhesions (FAs), and the integration of multiple signaling pathways, including extracellular signal-regulated kinase (ERK), wingless/integrated (WNT), and Hippo signaling. Furthermore, emerging evidence substantiates the implication of long non-coding RNAs (lncRNAs) as mechanosensitive molecules in cellular mechanotransduction. In this review, we discuss the mechanisms through which YAP/TAZ and lncRNAs serve as effectors in responding to mechanical stimuli. Additionally, we summarize and elaborate on the crucial signal molecules involved in mechanotransduction.




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


[1]Aguirre GhisoJA, FaríasEF, AlonsoDF, et al., 1997. A phospholipase D and protein kinase C inhibitor blocks the spreading of murine mammary adenocarcinoma cells altering f-actin and β1-integrin point contact distribution. Int J Cancer, 71(5):881-890.

[2]AharonovA, ShakkedA, UmanskyKB, et al., 2020. ERBB2 drives YAP activation and EMT-like processes during cardiac regeneration. Nat Cell Biol, 22(11):1346-1356.

[3]AhmadUS, UttagomolJ, WanH, 2022. The regulation of the Hippo pathway by intercellular junction proteins. Life, 12(11):1792.

[4]AragonaM, PancieraT, ManfrinA, et al., 2013. A mechanical checkpoint controls multicellular growth through YAP/TAZ regulation by actin-processing factors. Cell, 154(5):1047-1059.

[5]BertrandAT, ZiaeiS, EhretC, et al., 2014. Cellular microenvironments reveal defective mechanosensing responses and elevated YAP signaling in LMNA-mutated muscle precursors. J Cell Sci, 127(13):2873-2884.

[6]BruyèreC, VersaevelM, MohammedD, et al., 2019. Actomyosin contractility scales with myoblast elongation and enhances differentiation through YAP nuclear export. Sci Rep, 9:15565.

[7]CalvoF, EgeN, Grande-GarciaA, et al., 2013. Mechanotransduction and YAP-dependent matrix remodelling is required for the generation and maintenance of cancer-associated fibroblasts. Nat Cell Biol, 15(6):637-646.

[8]ChangL, AzzolinL, di BiagioD, et al., 2018. The SWI/SNF complex is a mechanoregulated inhibitor of YAP and TAZ. Nature, 563(7730):265-269.

[9]ChenZ, LuoQ, LinCC, et al., 2016. Simulated microgravity inhibits osteogenic differentiation of mesenchymal stem cells via depolymerizing F-actin to impede TAZ nuclear translocation. Sci Rep, 6:30322.

[10]ChoiSW, KimHW, NamJW, 2019. The small peptide world in long noncoding RNAs. Brief Bioinform, 20(5):1853-1864.

[11]ChuGL, ZhangWD, ZhouPH, et al., 2021. Substrate topography regulates differentiation of annulus fibrosus-derived stem cells via CAV1-YAP-mediated mechanotransduction. ACS Biomater Sci Eng, 7(3):862-871.

[12]CoreyDP, HudspethAJ, 1979. Ionic basis of the receptor potential in a vertebrate hair cell. Nature, 281(5733):675-677.

[13]CosteB, MathurJ, SchmidtM, et al., 2010. Piezo1 and Piezo2 are essential components of distinct mechanically activated cation channels. Science, 330(6000):55-60.

[14]DischerDE, JanmeyP, WangYL, 2005. Tissue cells feel and respond to the stiffness of their substrate. Science, 310(5751):1139-1143.

[15]DonnalojaF, CarnevaliF, JacchettiE, et al., 2020. Lamin A/C mechanotransduction in laminopathies. Cells, 9(5):1306.

[16]DriscollTP, CosgroveBD, HeoSJ, et al., 2015. Cytoskeletal to nuclear strain transfer regulates YAP signaling in mesenchymal stem cells. Biophys J, 108(12):2783-2793.

[17]DupontS, 2016. Role of YAP/TAZ in cell-matrix adhesion-mediated signalling and mechanotransduction. Exp Cell Res, 343(1):42-53.

[18]DupontS, MorsutL, AragonaM, et al., 2011. Role of YAP/TAZ in mechanotransduction. Nature, 474(7350):179-183.

[19]ElbediwyA, VanyaiH, Diaz-de-la-LozaMDC, et al., 2018. Enigma proteins regulate YAP mechanotransduction. J Cell Sci, 131(22):jcs221788.

[20]Elosegui-ArtolaA, AndreuI, BeedleAEM, et al., 2017. Force triggers YAP nuclear entry by regulating transport across nuclear pores. Cell, 171(6):1397-1410.e14.

[21]EnglerA, BacakovaL, NewmanC, et al., 2004. Substrate compliance versus ligand density in cell on gel responses. Biophys J, 86(1 Pt 1):617-628.

[22]EnglerAJ, SenS, SweeneyHL, et al., 2006. Matrix elasticity directs stem cell lineage specification. Cell, 126(4):677-689.

[23]FengXD, DegeseMS, Iglesias-BartolomeR, et al., 2014. Hippo-independent activation of YAP by the GNAQ uveal melanoma oncogene through a trio-regulated Rho GTPase signaling circuitry. Cancer Cell, 25(6):831-845.

[24]FletcherDA, MullinsRD, 2010. Cell mechanics and the cytoskeleton. Nature, 463(7280):485-492.

[25]FurukawaKT, YamashitaK, SakuraiN, et al., 2017. The epithelial circumferential actin belt regulates YAP/TAZ through nucleocytoplasmic shuttling of Merlin. Cell Rep, 20(6):1435-1447.

[26]GaoZR, LingXY, ShiCY, et al., 2022. Tumor immune checkpoints and their associated inhibitors. J Zhejiang Univ-Sci B (Biomed & Biotechnol), 23(10):823-843.

[27]GoldmannWH, 2012. Mechanotransduction in cells. Cell Biol Int, 36(6):567-570.

[28]GoldmannWH, 2014. Vinculin-p130Cas interaction is critical for focal adhesion dynamics and mechano-transduction. Cell Biol Int, 38(3):283-286.

[29]GuilluyC, OsborneLD, van LandeghemL, et al., 2014. Isolated nuclei adapt to force and reveal a mechanotransduction pathway in the nucleus. Nat Cell Biol, 16(4):376-381.

[30]GuvendirenM, BurdickJA, 2012. Stiffening hydrogels to probe short- and long-term cellular responses to dynamic mechanics. Nat Commun, 3:792.

[31]HoffmanLM, SmithMA, JensenCC, et al., 2020. Mechanical stress triggers nuclear remodeling and the formation of transmembrane actin nuclear lines with associated nuclear pore complexes. Mol Biol Cell, 31(16):1774-1787.

[32]HuJ, LiaoHJ, MaZB, et al., 2016. Focal adhesion kinase signaling mediated the enhancement of osteogenesis of human mesenchymal stem cells induced by extracorporeal shockwave. Sci Rep, 6:20875.

[33]HuLH, WuW, ZouJ, 2022. Circular RNAs: typical biomarkers for bone-related diseases. J Zhejiang Univ-Sci B (Biomed & Biotechnol), 23(12):975-988.

[34]HumphriesJD, ByronA, HumphriesMJ, 2006. Integrin ligands at a glance. J Cell Sci, 119(Pt 19):3901-3903.

[35]IngberDE, 1997. Tensegrity: the architectural basis of cellular mechanotransduction. Annu Rev Physiol, 59:575-599.

[36]JanotaCS, Calero-CuencaFJ, GomesER, 2020. The role of the cell nucleus in mechanotransduction. Curr Opin Cell Biol, 63:204-211.

[37]JiaQ, ZhouW, YaoW, et al., 2016. Downregulation of YAP-dependent Nupr1 promotes tumor-repopulating cell growth in soft matrices. Oncogenesis, 5(4):e220.

[38]JinP, JanLY, JanYN, 2020. Mechanosensitive ion channels: structural features relevant to mechanotransduction mechanisms. Annu Rev Neurosci, 43:207-229.

[39]Jojoa-CruzS, SaotomeK, TsuiCCA, et al., 2022. Structural insights into the Venus flytrap mechanosensitive ion channel Flycatcher1. Nat Commun, 13:850.

[40]JuC, LiuRF, ZhangYW, et al., 2019. Mesenchymal stem cell-associated lncRNA in osteogenic differentiation. Biomed Pharmacother, 115:108912.

[41]KefauverJM, WardAB, PatapoutianA, 2020. Discoveries in structure and physiology of mechanically activated ion channels. Nature, 587(7835):567-576.

[42]KimJ, KimYH, KimJ, et al., 2017. YAP/TAZ regulates sprouting angiogenesis and vascular barrier maturation. J Clin Invest, 127(9):3441-3461.

[43]KimNG, GumbinerBM, 2015. Adhesion to fibronectin regulates Hippo signaling via the FAK-Src-PI3K pathway. J Cell Biol, 210(3):503-515.

[44]KurodaM, UedaK, KiokaN, 2018. Vinexin family (SORBS) proteins regulate mechanotransduction in mesenchymal stem cells. Sci Rep, 8:11581.

[45]KurotsuS, SadahiroT, FujitaR, et al., 2020. Soft matrix promotes cardiac reprogramming via inhibition of YAP/TAZ and suppression of fibroblast signatures. Stem Cell Rep, 15(3):612-628.

[46]LeuchtP, KimJB, CurreyJA, et al., 2007. FAK-mediated mechanotransduction in skeletal regeneration. PLoS ONE, 2(4):e390.

[47]LiRH, TianT, GeQW, et al., 2021. A phosphatidic acid-binding lncRNA SNHG9 facilitates LATS1 liquid-liquid phase separation to promote oncogenic YAP signaling. Cell Res, 31(10):1088-1105.

[48]LiuCZ, GaoXC, LiYH, et al., 2022. The mechanosensitive lncRNA Neat1 promotes osteoblast function through paraspeckle-dependent Smurf1 mRNA retention. Bone Res, 10:18.

[49]LiuL, LiuMC, XieDF, et al., 2021. Role of the extracellular matrix and YAP/TAZ in cell reprogramming. Differentiation, 122:1-6.

[50]LiuOX, LinLB, ChewT, et al., 2018. ZO-2 induces cytoplasmic retention of YAP by promoting a LATS1-ZO-2-YAP complex at tight junctions. bioRxiv, preprint.

[51]LiuQ, HuXQ, ZhangX, et al., 2016. The TMSB4 pseudogene lncRNA functions as a competing endogenous RNA to promote cartilage degradation in human osteoarthritis. Mol Ther, 24(10):1726-1733.

[52]LiuX, HouWQ, HeL, et al., 2019. AMOT130/YAP pathway in topography-induced BMSC osteoblastic differentiation. Colloids Surf B Biointerfaces, 182:110332.

[53]López-GayJM, NunleyH, SpencerM, et al., 2020. Apical stress fibers enable a scaling between cell mechanical response and area in epithelial tissue. Science, 370(6514):eabb2169.

[54]MantellaLE, SinghKK, SandhuP, et al., 2017. Fingerprint of long non-coding RNA regulated by cyclic mechanical stretch in human aortic smooth muscle cells: implications for hypertension. Mol Cell Biochem, 435(1-2):163-173.

[55]MaurerM, LammerdingJ, 2019. The driving force: nuclear mechanotransduction in cellular function, fate, and disease. Annu Rev Biomed Eng, 21:443-468.

[56]MeliVS, VeerasubramanianPK, DowningTL, et al., 2023. Mechanosensation to inflammation: roles for YAP/TAZ in innate immune cells. Sci Signal, 16(783):eadc9656.

[57]MengZP, QiuYJ, LinKC, et al., 2018. RAP2 mediates mechanoresponses of the Hippo pathway. Nature, 560(7720):655-660.

[58]Moreno-VicenteR, PavónDM, Martín-PaduraI, et al., 2018. Caveolin-1 modulates mechanotransduction responses to substrate stiffness through actin-dependent control of YAP. Cell Rep, 25(6):1622-1635.e6.

[59]MorganJT, MurphyCJ, RussellP, 2013. What do mechanotransduction, Hippo, Wnt, and TGFβ have in common? YAP and TAZ as key orchestrating molecules in ocular health and disease. Exp Eye Res, 115:1-12.

[60]NardoneG, Oliver-de la CruzJ, VrbskyJ, et al., 2017. YAP regulates cell mechanics by controlling focal adhesion assembly. Nat Commun, 8:15321.

[61]NiuLM, LouFZ, SunY, et al., 2020. A micropeptide encoded by lncRNA MIR155HG suppresses autoimmune inflammation via modulating antigen presentation. Sci Adv, 6(21):eaaz2059.

[62]OwensDJ, FischerM, JabreS, et al., 2020. Lamin mutations cause increased YAP nuclear entry in muscle stem cells. Cells, 9(4):816.

[63]PancieraT, CitronA, di BiagioD, et al., 2020. Reprogramming normal cells into tumour precursors requires ECM stiffness and oncogene-mediated changes of cell mechanical properties. Nat Mater, 19(7):797-806.

[64]PatwardhanS, MahadikP, ShettyO, et al., 2021. ECM stiffness-tuned exosomes drive breast cancer motility through thrombospondin-1. Biomaterials, 279:121185.

[65]Puklin-FaucherE, SheetzMP, 2009. The mechanical integrin cycle. J Cell Sci, 122(2):179-186.

[66]QuL, HeXY, TangQ, et al., 2022. Iron metabolism, ferroptosis, and lncRNA in cancer: knowns and unknowns. J Zhejiang Univ-Sci B (Biomed & Biotechnol), 23(10):844-862

[67]SchwartzC, FischerM, MamchaouiK, et al., 2017. Lamins and nesprin-1 mediate inside-out mechanical coupling in muscle cell precursors through FHOD1. Sci Rep, 7:1253.

[68]SeetharamanS, Etienne-MannevilleS, 2018. Integrin diversity brings specificity in mechanotransduction. Biol Cell, 110(3):49-64.

[69]ShevelyovYY, UlianovSV, 2019. The nuclear lamina as an organizer of chromosome architecture. Cells, 8(2):136.

[70]Sladitschek-MartensHL, GuarnieriA, BrumanaG, et al., 2022. YAP/TAZ activity in stromal cells prevents ageing by controlling cGAS-STING. Nature, 607(7920):790-798.

[71]SolonJ, LeventalI, SenguptaK, et al., 2007. Fibroblast adaptation and stiffness matching to soft elastic substrates. Biophys J, 93(12):4453-4461.

[72]SunYB, YongKMA, Villa-DiazLG, et al., 2014. Hippo/YAP-mediated rigidity-dependent motor neuron differentiation of human pluripotent stem cells. Nat Mater, 13(6):599-604.

[73]TamadaM, SheetzMP, SawadaY, 2004. Activation of a signaling cascade by cytoskeleton stretch. Dev Cell, 7(5):709-718.

[74]TanoueT, TakeichiM, 2004. Mammalian Fat1 cadherin regulates actin dynamics and cell‒cell contact. J Cell Biol, 165(4):517-528.

[75]TeeSY, FuJP, ChenCS, et al., 2011. Cell shape and substrate rigidity both regulate cell stiffness. Biophys J, 100(5):L25-L27.

[76]TodorovskiV, FoxAH, ChoiYS, 2020. Matrix stiffness-sensitive long noncoding RNA NEAT1 seeded paraspeckles in cancer cells. Mol Biol Cell, 31(16):1654-1662.

[77]TschumperlinDJ, 2011. Mechanotransduction. Compr Physiol, 1(2):1057-1073.

[78]UrayIP, UrayK, 2021. Mechanotransduction at the plasma membrane-cytoskeleton interface. Int J Mol Sci, 22(21):11566.

[79]VirdiJK, PetheP, 2021. Biomaterials regulate mechanosensors YAP/TAZ in stem cell growth and differentiation. Tissue Eng Regen Med, 18(2):199-215.

[80]WangJ, ZhangYF, ZhangN, et al., 2015. An updated review of mechanotransduction in skin disorders: transcriptional regulators, ion channels, and microRNAs. Cell Mol Life Sci, 72(11):2091-2106.

[81]WangKC, YehYT, NguyenP, et al., 2016. Flow-dependent YAP/TAZ activities regulate endothelial phenotypes and atherosclerosis. Proc Natl Acad Sci USA, 113(41):11525-11530.

[82]WangL, LuoJY, LiBC, et al., 2016. Integrin-YAP/TAZ-JNK cascade mediates atheroprotective effect of unidirectional shear flow. Nature, 540(7634):579-582.

[83]WuJJ, ZhaoJ, SunL, et al., 2018. Long non-coding RNA H19 mediates mechanical tension-induced osteogenesis of bone marrow mesenchymal stem cells via FAK by sponging miR-138. Bone, 108:62-70.

[84]WuLY, HanCL, LinHH, et al., 2022. Ha-RasV12-induced multilayer cellular aggregates is mediated by Rac1 activation rather than YAP activation. Biomedicines, 10(5):977.

[85]WuP, MoYZ, PengM, et al., 2020. Emerging role of tumor-related functional peptides encoded by lncRNA and circRNA. Mol Cancer, 19:22.

[86]XuJJ, SunMY, TanY, et al., 2017. Effect of matrix stiffness on the proliferation and differentiation of umbilical cord mesenchymal stem cells. Differentiation, 96:30-39.

[87]XuXC, ZhangY, WangX, et al., 2021. Substrate stiffness drives epithelial to mesenchymal transition and proliferation through the NEAT1-Wnt/β-catenin pathway in liver cancer. Int J Mol Sci, 22(21):12066.

[88]YamashiroY, ThangBQ, RamirezK, et al., 2020. Matrix mechanotransduction mediated by thrombospondin-1/integrin/YAP in the vascular remodeling. Proc Natl Acad Sci USA, 117(18):9896-9905.

[89]YuFX, ZhaoB, PanupinthuN, et al., 2012. Regulation of the Hippo-YAP pathway by G-protein-coupled receptor signaling. Cell, 150(4):780-791.

[90]YuiS, AzzolinL, MaimetsM, et al., 2018. YAP/TAZ-dependent reprogramming of colonic epithelium links ECM remodeling to tissue regeneration. Cell Stem Cell, 22(1):35-49.e7.

[91]ZanconatoF, CordenonsiM, PiccoloS, 2016. YAP/TAZ at the roots of cancer. Cancer Cell, 29(6):783-803.

[92]ZhangHL, LiuG, MaoX, et al., 2022. LncRNA MEG3 induces endothelial differentiation of mouse derived adipose-derived stem cells by targeting miR-145-5p/KLF4. Mol Biol Rep, 49(9):8495-8505.

[93]ZhangQ, LinSY, LiaoJF, et al., 2018. Physical cues drive chondrogenic differentiation. Curr Stem Cell Res Ther, 13(7):576-582.

[94]ZhaoB, WeiXM, LiWQ, et al., 2007. Inactivation of YAP oncoprotein by the Hippo pathway is involved in cell contact inhibition and tissue growth control. Genes Dev, 21(21):2747-2761.

[95]ZhaoB, LiL, WangL, et al., 2012. Cell detachment activates the Hippo pathway via cytoskeleton reorganization to induce anoikis. Genes Dev, 26(1):54-68.

[96]ZhengLJ, LuoCY, YangN, et al., 2022. Ionizing radiation-induced long noncoding RNA CRYBG3 regulates YAP/TAZ through mechanotransduction. Cell Death Dis, 13(3):209.

[97]ZhuGZ, ZengCJ, QianYP, et al., 2021. Tensile strain promotes osteogenic differentiation of bone marrow mesenchymal stem cells through upregulating lncRNA-MEG3. Histol Histopathol, 36(9):939-946.

[98]ZhuHY, LiJ, LiYZ, et al., 2021. Glucocorticoid counteracts cellular mechanoresponses by LINC01569-dependent glucocorticoid receptor-mediated mRNA decay. Sci Adv, 7(9):eabd9923.

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