Generic placeholder image

Recent Patents on Anti-Cancer Drug Discovery

Editor-in-Chief

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

Research Article

LncRNA FAM83H-AS1 Contributes to the Radio-resistance and Proliferation in Liver Cancer through Stability FAM83H Protein

Author(s): Xiaocong Jiang, Yuhong Lan, Yingchun Zhang, Yuhong Dong* and Ting Song*

Volume 19, Issue 3, 2024

Published on: 15 May, 2023

Page: [316 - 327] Pages: 12

DOI: 10.2174/1574892818666230427164227

Price: $65

Abstract

Background: Liver cancer (LC) is one of China's most common malignant tumors, with a high mortality rate, ranking third leading cause of death after gastric and esophageal cancer. Recent patents propose the LncRNA FAM83H-AS1 has been verified to perform a crucial role in the progression of LC. LncRNA FAM83H-AS1 has been verified to perform a crucial role in the progression of LC. However, the concrete mechanism remains to be pending further investigation.

Objective: This study aimed to explore the embedding mechanism of FAM83H-AS1 molecules in terms of radio sensitivity of LC and provide potentially effective therapeutic targets for LC therapy.

Methods: Quantitative real-time PCR (qRT-PCR) was conducted to measure the transcription levels of genes. Proliferation was determined via CCK8 and colony formation assays. Western blot was carried out to detect the relative protein expression. A xenograft mouse model was constructed to investigate the effect of LncRNA FAM83H-AS1 on tumor growth and radio-sensitivity in vivo.

Results: The levels of lncRNA FAM83H-AS1 were remarkably increased in LC. Knockdown of FAM83H-AS1 inhibited LC cell proliferation and colony survival fraction. Deletion of FAM83H-AS1 increased the sensitivity of LC cells to 4 Gy of X-ray radiation. In the xenograft model, radiotherapy combined with FAM83H-AS1 silencing significantly reduced tumor volume and weight. Overexpression of FAM83H reversed the effects of FAM83H-AS1 deletion on proliferation and colony survival fraction in LC cells. Moreover, the over-expressing of FAM83H also restored the tumor volume and weight reduction caused by the knockdown of FAM83H-AS1 or radiation in the xenograft model.

Conclusion: Knockdown of lncRNA FAM83H-AS1 inhibited LC growth and enhanced radiosensitivity in LC. It has the potential to be a promising target for LC therapy.

[1]
Kumar V, Kaur M, Guleria P. Nanomaterials for diagnosis and treatment of lung cancer: A review of recent patents. Recent Patents Anticancer Drug Discov 2023; 18(2): 114-24.
[http://dx.doi.org/10.2174/1574892817666220629104641] [PMID: 35770413]
[2]
Siegel RL, Miller KD, Jemal A. Cancer statistics, 2019. CA Cancer J Clin 2019; 69(1): 7-34.
[http://dx.doi.org/10.3322/caac.21551] [PMID: 30620402]
[3]
A tumor microenvironment-responsive pezopani nano-delivery system and its preparation method. Chinese patent: CN202211278269.7 2023.01.06,
[4]
Liu T, Chi H, Chen J, et al. Curcumin suppresses proliferation and in vitro invasion of human prostate cancer stem cells by ceRNA effect of miR-145 and lncRNA-ROR. Gene 2017; 631: 29-38.
[http://dx.doi.org/10.1016/j.gene.2017.08.008] [PMID: 28843521]
[5]
Mottet N, Bellmunt J, Bolla M, et al. EAU-ESTRO-SIOG guidelines on prostate cancer. Part 1: screening, diagnosis, and local treatment with curative intent. Eur Urol 2017; 71(4): 618-29.
[http://dx.doi.org/10.1016/j.eururo.2016.08.003] [PMID: 27568654]
[6]
Chiyomaru T, Fukuhara S, Saini S, et al. Long non-coding RNA HOTAIR is targeted and regulated by miR-141 in human cancer cells. J Biol Chem 2014; 289(18): 12550-65.
[http://dx.doi.org/10.1074/jbc.M113.488593] [PMID: 24616104]
[7]
Hirata H, Hinoda Y, Shahryari V, et al. Long noncoding RNA MALAT1 promotes aggressive renal cell carcinoma through Ezh2 and interacts with miR-205. Cancer Res 2015; 75(7): 1322-31.
[http://dx.doi.org/10.1158/0008-5472.CAN-14-2931] [PMID: 25600645]
[8]
Qiao HP, Gao WS, Huo JX, Yang ZS. Long non-coding RNA GAS5 functions as a tumor suppressor in renal cell carcinoma. Asian Pac J Cancer Prev 2013; 14(2): 1077-82.
[http://dx.doi.org/10.7314/APJCP.2013.14.2.1077] [PMID: 23621190]
[9]
Yang P, Yang Y, An W, et al. The long noncoding RNA-ROR promotes the resistance of radiotherapy for human colorectal cancer cells by targeting the p53/miR-145 pathway. J Gastroenterol Hepatol 2017; 32(4): 837-45.
[http://dx.doi.org/10.1111/jgh.13606] [PMID: 27696511]
[10]
Yabushita S, Fukamachi K, Tanaka H, et al. Metabolomic and transcriptomic profiling of human K- ras oncogene transgenic rats with pancreatic ductal adenocarcinomas. Carcinogenesis 2013; 34(6): 1251-9.
[http://dx.doi.org/10.1093/carcin/bgt053] [PMID: 23393225]
[11]
Iyer MK, Niknafs YS, Malik R, et al. The landscape of long noncoding RNAs in the human transcriptome. Nat Genet 2015; 47(3): 199-208.
[http://dx.doi.org/10.1038/ng.3192] [PMID: 25599403]
[12]
Zhu P, Wang Y, Wu J, et al. LncBRM initiates YAP1 signalling activation to drive self-renewal of liver cancer stem cells. Nat Commun 2016; 7: 13608.
[http://dx.doi.org/10.1038/ncomms13608]
[13]
Deva MRAK, Patel K, Korivi JS, et al. Identification of lnc RNA s associated with early‐stage breast cancer and their prognostic implications. Mol Oncol 2019; 13(6): 1342-55.
[http://dx.doi.org/10.1002/1878-0261.12489] [PMID: 30959550]
[14]
Wei R, Chen Y, Zhao Z, Gu Q, Wu J. LncRNA FAM83H‐AS1 induces nucleus pulposus cell growth via targeting the Notch signaling pathway. J Cell Physiol 2019; 234(12): 22163-71.
[http://dx.doi.org/10.1002/jcp.28780] [PMID: 31102263]
[15]
Yang L, Cui J, Wang Y, et al. FAM83H-AS1 is upregulated and predicts poor prognosis in colon cancer. Biomed Pharmacother 2019; 118: 109342.
[http://dx.doi.org/10.1016/j.biopha.2019.109342]
[16]
Han C, Fu Y, Zeng N, Yin J, Li Q. LncRNA FAM83H-AS1 promotes triple-negative breast cancer progression by regulating the miR-136-5p/metadherin axis. Aging 2020; 12(4): 3594-616.
[http://dx.doi.org/10.18632/aging.102832] [PMID: 32074085]
[17]
Wang B, Guan G, Zhao D. Silence of FAM83H-AS1 promotes chemosensitivity of gastric cancer through Wnt/β-catenin signaling pathway. Biomed Pharmacother 2020; 125: 109961.
[http://dx.doi.org/10.1016/j.biopha.2020.109961]
[18]
Dou Q, Xu Y, Zhu Y, Hu Y, Yan Y, Yan H. LncRNA FAM83H-AS1 contributes to the radioresistance, proliferation, and metastasis in ovarian cancer through stabilizing HuR protein. Eur J Pharmacol 2019; 852: 134-41.
[http://dx.doi.org/10.1016/j.ejphar.2019.03.002] [PMID: 30831080]
[19]
Snijders AM, Lee SY, Hang B, Hao W, Bissell MJ, Mao JH. FAM83 family oncogenes are broadly involved in human cancers: An integrative multi-omics approach. Mol Oncol 2017; 11(2): 167-79.
[http://dx.doi.org/10.1002/1878-0261.12016] [PMID: 28078827]
[20]
Cipriano R, Miskimen KLS, Bryson BL, Foy CR, Bartel CA, Jackson MW. Conserved oncogenic behavior of the FAM83 family regulates MAPK signaling in human cancer. Mol Cancer Res 2014; 12(8): 1156-65.
[http://dx.doi.org/10.1158/1541-7786.MCR-13-0289] [PMID: 24736947]
[21]
Kim JW, Lee SK, Lee ZH, et al. FAM83H mutations in families with autosomal-dominant hypocalcified amelogenesis imperfecta. Am J Hum Genet 2008; 82(2): 489-94.
[http://dx.doi.org/10.1016/j.ajhg.2007.09.020] [PMID: 18252228]
[22]
Urzúa B, Martínez C, Ortega-Pinto A, et al. Novel missense mutation of the FAM83H gene causes retention of amelogenin and a mild clinical phenotype of hypocalcified enamel. Arch Oral Biol 2015; 60(9): 1356-67.
[http://dx.doi.org/10.1016/j.archoralbio.2015.06.016] [PMID: 26142250]
[23]
Nalla AK, Williams TF, Collins CP, Rae DT, Trobridge GD. Lentiviral vector-mediated insertional mutagenesis screen identifies genes that influence androgen independent prostate cancer progression and predict clinical outcome. Mol Carcinog 2016; 55(11): 1761-71.
[http://dx.doi.org/10.1002/mc.22425] [PMID: 26512949]
[24]
Bearz A, Cecco S, Francescon S, Re FL, Corona G, Baldo P. Safety profiles and pharmacovigilance considerations for recently patented anticancer drugs: Lung cancer. Recent Patents Anticancer Drug Discov 2019; 14(3): 242-57.
[http://dx.doi.org/10.2174/1574892814666190726124735] [PMID: 31362665]
[25]
Xiu D, Liu L, Cheng M, Sun X, Ma X. Knockdown of lncRNA TUG1 enhances radiosensitivity of prostate cancer via the TUG1/miR-139-5p/SMC1A axis. OncoTargets Ther 2020; 13: 2319-31.
[http://dx.doi.org/10.2147/OTT.S236860] [PMID: 32256083]
[26]
Gao F, Cai Y, Kapranov P, Xu D. Reverse-genetics studies of lncRNAs-what we have learnt and paths forward. Genome Biol 2020; 21(1): 93.
[http://dx.doi.org/10.1186/s13059-020-01994-5] [PMID: 32290841]
[27]
Wu YY, Kuo HC. Functional roles and networks of non-coding RNAs in the pathogenesis of neurodegenerative diseases. J Biomed Sci 2020; 27(1): 49.
[http://dx.doi.org/10.1186/s12929-020-00636-z] [PMID: 32264890]
[28]
Flippot R, Beinse G, Boilève A, Vibert J, Malouf GG. Long non-coding RNAs in genitourinary malignancies: A whole new world. Nat Rev Urol 2019; 16(8): 484-504.
[http://dx.doi.org/10.1038/s41585-019-0195-1] [PMID: 31110275]
[29]
Peng W-X, Koirala P, Mo Y-Y. LncRNA-mediated regulation of cell signaling in cancer. Oncogene 2017; 36(41): 5661-7.
[http://dx.doi.org/10.1038/onc.2017.184] [PMID: 28604750]
[30]
Hua JT, Ahmed M, Guo H, et al. Risk SNP-mediated promoter-enhancer switching drives prostate cancer through lncRNA PCAT19. Cell 2018; 174(3): 564-575.e18.
[http://dx.doi.org/10.1016/j.cell.2018.06.014] [PMID: 30033362]
[31]
Chen Y, Zitello E, Guo R, Deng Y. The function of LncRNAs and their role in the prediction, diagnosis, and prognosis of lung cancer. Clin Transl Med 2021; 11(4): e367.
[http://dx.doi.org/10.1002/ctm2.367] [PMID: 33931980]
[32]
Lingadahalli S, Jadhao S, Sung YY, et al. LINC00844Novel lncRNA regulates lung cancer cell migration and invasion through AR signaling. Molecular cancer research. MCR 2018; 16: 1865-78.
[http://dx.doi.org/10.1158/1541-7786.MCR-18-0087] [PMID: 30115758]
[33]
Hua Q, Jin M, Mi B, et al. LINC01123, a c-Myc-activated long non-coding RNA, promotes proliferation and aerobic glycolysis of non-small cell lung cancer through miR-199a-5p/c-Myc axis. J Hematol Oncol 2019; 12(1): 91.
[http://dx.doi.org/10.1186/s13045-019-0773-y] [PMID: 31488218]

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