Login Register Cart 0
Generic placeholder image

Recent Patents on Anti-Cancer Drug Discovery

Editor-in-Chief

ISSN (Print): 1574-8928
ISSN (Online): 2212-3970

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Research Article

LncRNA TCTN2 Promotes the Malignant Development of Hepatocellular Carcinoma via Regulating mIR-1285-3p/ARF6 Axis

Author(s): Qian Liu, Chunfu Zhu and Yanfen Dong*

Volume 18, Issue 4, 2023

Published on: 15 November, 2022

Page: [517 - 527] Pages: 11

DOI: 10.2174/1574892818666221019163656

Price: $65

Abstract

Background: Hepatocellular carcinoma (HCC) is one of the most life-threatening malignant diseases. TCTN2 protein participates in tumorigenesis and development. However, whether lncRNA TCTN2 is associated with HCC pathogenesis remains unclear.

Methods: The expression of lncRNA, TCTN2, miR-1285-3p, and ARF6 in HCC tissues and cells was detected by a quantitative Real-Time PCR (qRT-PCR) assay. lncRNA TCTN2-specific shRNA was transfected into HCC cells, and a functional investigation was performed. The direct interactions between lncRNA TCTN2 and miR-1285-3p and ARF6 were verified by dualluciferase reporter gene assay. A rescue experiment was performed to confirm the role of miR- 1285-3p/ARF6 in association with lncRNA TCTN2.

Results: LncRNA TCTN2 exhibited a high expression in HCC tumor tissues and cell lines. Knockdown of lncRNA TCTN2 suppressed cell proliferation and induced cell cycle arrest and apoptosis through regulating Cyclin D1/p21 and Bax/Bcl-2 signals. Meanwhile, the knockdown of lncRNA TCTN2 inhibited HCC cell migration and invasion through upregulating MMP2/MMP9. Mechanistic investigation revealed that lncRNA TCTN2 upregulated the expression of ARF6 via sponging miR-1285-3p. Rescue experiments indicated that miR-1285-3p inhibitor reversed the antitumor effects of lncRNA TCTN2 and ARF6 knockdown inhibited the progression of HCC.

Conclusion: Our results suggested that the knockdown of lncRNA TCTN2 inhibited HCC development by regulating the miR-1285-3p/ARF6 axis, implying that the lncRNA TCTN2 is upregulated in HCC and may serve as a diagnostic biomarker in HCC. Furthermore, it may demonstrate an important value for the clinical treatment of patients with HCC.

« Previous Next »
[1]
Schmieder R, Puehler F, Neuhaus R, et al. Allosteric MEK1/2 inhibitor refametinib (BAY 86-9766) in combination with sorafenib exhibits antitumor activity in preclinical murine and rat models of hepatocellular carcinoma. Neoplasia 2013; 15(10): 1161-IN24.
[http://dx.doi.org/10.1593/neo.13812] [PMID: 24204195]
[2]
Su JC, Tseng PH, Wu SH, et al. SC-2001 overcomes STAT3-mediated sorafenib resistance through RFX-1/SHP-1 activation in hepatocellular carcinoma. Neoplasia 2014; 16(7): 595-605.
[http://dx.doi.org/10.1016/j.neo.2014.06.005] [PMID: 25047655]
[3]
Llovet JM. Time to evolve trial design after everolimus failure. Nat Rev Clin Oncol 2014; 11(9): 506-7.
[http://dx.doi.org/10.1038/nrclinonc.2014.136] [PMID: 25091613]
[4]
Singal A, Volk ML, Waljee A, et al. Meta-analysis: Surveillance with ultrasound for early-stage hepatocellular carcinoma in patients with cirrhosis. Aliment Pharmacol Ther 2009; 30(1): 37-47.
[http://dx.doi.org/10.1111/j.1365-2036.2009.04014.x] [PMID: 19392863]
[5]
El-Serag HB, Rudolph KL. Hepatocellular carcinoma: Epidemiology and molecular carcinogenesis. Gastroenterology 2007; 132(7): 2557-76.
[http://dx.doi.org/10.1053/j.gastro.2007.04.061] [PMID: 17570226]
[6]
Llovet JM, Ricci S, Mazzaferro V, et al. Sorafenib in advanced hepatocellular carcinoma. N Engl J Med 2008; 359(4): 378-90.
[http://dx.doi.org/10.1056/NEJMoa0708857] [PMID: 18650514]
[7]
Colecchia A, Schiumerini R, Cucchetti A, et al. Prognostic factors for hepatocellular carcinoma recurrence. World J Gastroenterol 2014; 20(20): 5935-50.
[http://dx.doi.org/10.3748/wjg.v20.i20.5935] [PMID: 24876717]
[8]
Lee SC, Tan HT, Chung MC. Prognostic biomarkers for prediction of recurrence of hepatocellular carcinoma: Current status and future prospects. World J Gastroenterol 2014; 20(12): 3112-24.
[http://dx.doi.org/10.3748/wjg.v20.i12.3112] [PMID: 24696598]
[9]
Naeli P, Pourhanifeh MH, Karimzadeh MR, et al. Circular RNAs and gastrointestinal cancers: Epigenetic regulators with a prognostic and therapeutic role. Crit Rev Oncol Hematol 2020; 145: 102854.
[http://dx.doi.org/10.1016/j.critrevonc.2019.102854] [PMID: 31877535]
[10]
Fang Y, Fullwood MJ. Roles, functions, and mechanisms of long non-coding RNAs in cancer. Genomics Proteomics Bioinformatics 2016; 14(1): 42-54.
[http://dx.doi.org/10.1016/j.gpb.2015.09.006] [PMID: 26883671]
[11]
Chen X, Wang L, Wang H. LINC01638 lncRNA promotes cancer cell proliferation in hepatocellular carcinoma by increasing cancer cell glucose uptake. Oncol Lett 2019; 18(4): 3811-6.
[http://dx.doi.org/10.3892/ol.2019.10682] [PMID: 31516592]
[12]
Lei GL, Niu Y, Cheng SJ, et al. Upregulation of long noncoding RNA W42 promotes tumor development by binding with DBN1 in hepatocellular carcinoma. World J Gastroenterol 2021; 27(20): 2586-602.
[http://dx.doi.org/10.3748/wjg.v27.i20.2586] [PMID: 34092977]
[13]
Expression of Concern: Targetting an LncRNA P5848-ENO1 axis inhibits tumor growth in hepatocellular carcinoma. Biosci Rep 2020; 40(8): BSR-20180896_EOC. http://dx.doi.org/10.1042/BSR-20180896_EOC PMID: 32776151
[14]
Chen BW, Zhou Y, Wei T, et al. lncRNA‐POIR promotes epithelial–mesenchymal transition and suppresses sorafenib sensitivity simultaneously in hepatocellular carcinoma by sponging miR‐182‐5p. J Cell Biochem 2021; 122(1): 130-42.
[http://dx.doi.org/10.1002/jcb.29844] [PMID: 32951268]
[15]
He X, Zheng Y, Zhang Y, et al. Long non-coding RNA AK058003, as a precursor of miR-15a, interacts with HuR to inhibit the expression of γ-synuclein in hepatocellular carcinoma cells. Oncotarget 2017; 8(6): 9451-65.
[http://dx.doi.org/10.18632/oncotarget.14276] [PMID: 28035067]
[16]
Mao LH, Chen SY, Li XQ, et al. LncRNA-LALR1 upregulates small nucleolar RNA SNORD72 to promote growth and invasion of hepatocellular carcinoma. Aging 2020; 12(5): 4527-46.
[http://dx.doi.org/10.18632/aging.102907] [PMID: 32160589]
[17]
Hoon D, Lessard L. Long noncoding RNA (LNCRNA) as a biomarker and therapeutic marker in cancer. Hindawi 2017; 2017: 1-14.
[18]
Bai J, Liang P, Li Q, Feng R, Liu J. Cancer immunotherapy - immune checkpoint inhibitors in hepatocellular carcinoma. Recent Patents Anticancer Drug Discov 2021; 16(2): 239-48.
[http://dx.doi.org/10.2174/1574892816666210212145107] [PMID: 33583384]
[19]
Chen B, Lan J, Xiao Y, et al. Long noncoding RNA TP53TG1 suppresses the growth and metastasis of hepatocellular carcinoma by regulating the PRDX4/β-catenin pathway. Cancer Lett 2021; 513: 75-89.
[http://dx.doi.org/10.1016/j.canlet.2021.04.022] [PMID: 33957185]
[20]
Chen PP, Zhang ZS, Wu JC, Zheng JF, Lin F. LncRNA SNHG12 promotes proliferation and epithelial mesenchymal transition in hepatocellular carcinoma through targeting HEG1 via miR-516a-5p. Cell Signal 2021; 84: 109992.
[http://dx.doi.org/10.1016/j.cellsig.2021.109992] [PMID: 33774129]
[21]
Yu Y, Zhang L, Xu J. LncRNA BANCR promotes proliferation of hepatocellular carcinoma Huh-7 cells by activating Wnt/β-catenin signaling pathway. Minerva Gastroenterol 2022; 68(3): 341-3.
[22]
Lan C, Wang Y, Su X, Lu J, Ma S. LncRNA LINC00958 activates mTORC1/P70S6K signalling pathway to promote epithelial-mesenchymal transition process in the hepatocellular carcinoma. Cancer Invest 2021; 39(6-7): 539-49.
[http://dx.doi.org/10.1080/07357907.2021.1929282] [PMID: 33979257]
[23]
Han W, Wang Q, Zheng L, et al. The role of lncRNA ANRIL in the progression of hepatocellular carcinoma. J Pharm Pharmacol 2021; 73(8): 1033-8.
[http://dx.doi.org/10.1093/jpp/rgaa047] [PMID: 34111289]
[24]
Guan Q, Yuan B, Zhang X, Yan T, Li J, Xu W. Long non coding RNA DUXAP8 promotes tumorigenesis by regulating IGF1R via miR-9-3p in hepatocellular carcinoma. Exp Ther Med 2021; 22(1): 755.
[http://dx.doi.org/10.3892/etm.2021.10187] [PMID: 34035852]
[25]
Ren X, Wan C, Niu Y. Overexpression of lnc RNA TCTN 2 protects neurons from apoptosis by enhancing cell autophagy in spinal cord injury. FEBS Open Bio 2019; 9(7): 1223-31.
[http://dx.doi.org/10.1002/2211-5463.12651] [PMID: 31050183]
[26]
Tay Y, Rinn J, Pandolfi PP. The multilayered complexity of ceRNA crosstalk and competition. Nature 2014; 505(7483): 344-52.
[http://dx.doi.org/10.1038/nature12986] [PMID: 24429633]
[27]
Yang L, Li G, Gao Y, Ou N, Yu T, Ren S. lncRNA NR4A1AS upregulates miR-221 through demethylation to promote cell proliferation in oral squamous cell carcinoma. Cancer Manag Res 2020; 12: 5285-92.
[http://dx.doi.org/10.2147/CMAR.S241769] [PMID: 32753947]
[28]
Hou XY, Jiang G, Yang CS, Tang JQ, Wei ZP, Liu YQ. Application of nanotechnology in the diagnosis and therapy of hepatocellular carcinoma. Recent Patents Anticancer Drug Discov 2016; 11(3): 322-31.
[http://dx.doi.org/10.2174/1574892811666160309121035] [PMID: 26955964]
[29]
Zhang Y, Tang L. The application of lncRNAs in cancer treatment and diagnosis. Recent Patents Anticancer Drug Discov 2018; 13(3): 292-301.
[http://dx.doi.org/10.2174/1574892813666180226121819] [PMID: 29485010]
[30]
Yu L, Huo L, Shao X, Zhao J. lncRNA SNHG5 promotes cell proliferation, migration and invasion in oral squamous cell carcinoma by sponging miR-655-3p/FZD4 axis. Oncol Lett 2020; 20(6): 1.
[http://dx.doi.org/10.3892/ol.2020.12173] [PMID: 33093919]
[31]
Yao Y, Chen S, Lu N, Yin Y, Liu Z. LncRNA JPX overexpressed in oral squamous cell carcinoma drives malignancy via miR‐944/CDH2 axis. Oral Dis 2021; 27(4): 924-33.
[http://dx.doi.org/10.1111/odi.13626] [PMID: 32881231]
[32]
Yu Q, Du Y, Wang S, Zheng X. LncRNA PART1 promotes cell proliferation and inhibits apoptosis of oral squamous cell carcinoma by blocking EZH2 degradation. J Biochem 2021; 169(6): 721-30.
[http://dx.doi.org/10.1093/jb/mvab026] [PMID: 33725092]
[33]
Zhang P, Liu Y, Li C, Zhang L, Liu Q, Jiang T. LncRNA PAPAS promotes oral squamous cell carcinoma by upregulating transforming growth factorβ1. J Cell Biochem 2019; 120(9): 16120-7.
[http://dx.doi.org/10.1002/jcb.28893] [PMID: 31099126]
[34]
Zhang X, Guo B, Zhu Y, Xu W, Ning S, Liu L. Up-regulation of plasma lncRNA CACS15 distinguished early-stage oral squamous cell carcinoma patient. Oral Dis 2020; 26(8): 1619-24.
[http://dx.doi.org/10.1111/odi.13245] [PMID: 31793142]
[35]
Ma SQ, Wang YC, Li Y, Li XY, Yang J, Sheng YM. LncRNA XIST promotes proliferation and cisplatin resistance of oral squamous cell carcinoma by downregulating miR-27b-3p. J Biol Regul Homeost Agents 2020; 34(6): 1993-2001.
[PMID: 33191714]
[36]
Wang M, Wang L, He X, et al. lncRNA CCAT2 promotes radiotherapy resistance for human esophageal carcinoma cells via the miR 145/p70S6K1 and p53 pathway. Int J Oncol 2020; 56(1): 327-36.
[PMID: 31789385]
[37]
Wang X, Hao R, Wang F, Wang F. ZFAS1 promotes cisplatin resistance via suppressing miR-421 expression in oral squamous cell carcinoma. Cancer Manag Res 2020; 12: 7251-62.
[http://dx.doi.org/10.2147/CMAR.S248869] [PMID: 32884341]
[38]
Garcia-Gonzalo FR, Corbit KC, Sirerol-Piquer MS, et al. A transition zone complex regulates mammalian ciliogenesis and ciliary membrane composition. Nat Genet 2011; 43(8): 776-84.
[http://dx.doi.org/10.1038/ng.891] [PMID: 21725307]
[39]
Cano-Rodriguez D, Campagnoli S, Grandi A, et al. TCTN2: A novel tumor marker with oncogenic properties. Oncotarget 2017; 8(56): 95256-69.
[http://dx.doi.org/10.18632/oncotarget.20438] [PMID: 29221125]
[40]
Liu J, Yan J, Zhou C, Ma Q, Jin Q, Yang Z. miR-1285-3p acts as a potential tumor suppressor miRNA via downregulating JUN expression in hepatocellular carcinoma. Tumour Biol 2015; 36(1): 219-25.
[http://dx.doi.org/10.1007/s13277-014-2622-5] [PMID: 25230788]
[41]
Villanova L, Barbini C, Piccolo C, Boe A, De Maria R, Fiori ME. miR-1285-3p controls colorectal cancer proliferation and escape from apoptosis through DAPK2. Int J Mol Sci 2020; 21(7): 2423.
[http://dx.doi.org/10.3390/ijms21072423] [PMID: 32244500]
[42]
Hu XH, Dai J, Shang HL, Zhao ZX, Hao Y. miR-1285-3p is a potential prognostic marker in human osteosarcoma and functions as a tumor suppressor by targeting YAP1. Cancer Biomark 2019; 25(1): 1-10.
[43]
D’Souza-Schorey C, Chavrier P. ARF proteins: Roles in membrane traffic and beyond. Nat Rev Mol Cell Biol 2006; 7(5): 347-58.
[http://dx.doi.org/10.1038/nrm1910] [PMID: 16633337]
[44]
Donaldson JG. Multiple roles for Arf6: Sorting, structuring, and signaling at the plasma membrane. J Biol Chem 2003; 278(43): 41573-6.
[http://dx.doi.org/10.1074/jbc.R300026200] [PMID: 12912991]
[45]
Wang S, Wang T, Gu P. microRNA-145-5p inhibits migration, invasion, and metastasis in hepatocellular carcinoma by inhibiting ARF6. Cancer Manag Res 2021; 13: 3473-84.
[http://dx.doi.org/10.2147/CMAR.S300678] [PMID: 33907470]
[46]
Oskar S, Yilia P, Spatz JP, et al. Bottom-up assembly of biomedical relevant fully synthetic extracellular vesicles. Sci Adv 2021; 7(36): eabg6666.
[47]
Ashok B, Kirill O, Alan M, Damon P. ARF6 inhibitors and related methods. Patent JP2020531519A, 2021.

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy