LINC00839 Promotes Malignancy of Liver Cancer Via Binding FMNL2 Under Hypoxia

Overview

Journal Sci Rep

Specialty Science

Date 2022 Nov 6

PMID 36335129

Authors

Yangyi Xie

Hongsheng Lin

Wei Wei

Yinzhi Kong

Qiaoling Fang

Enran Chen

Jianghua Liu

Mingfen Li

Affiliations

Soon will be listed here.

Abstract

Liver cancer is one of the most common malignant tumors in the world and metastasis is the leading cause of death associated with liver cancer. Hypoxia is a common feature of solid tumors and enhances malignant character of cancer cells. However, the exact mechanisms involved in hypoxia-driven liver cancer progression and metastasis have not been well clarified so far. The aim of this study was to investigate the contribution of long non-coding RNA (lncRNA) in hypoxia promoting liver cancer progression. We screened and revealed LINC00839 as a novel hypoxia-responsive lncRNA in liver cancer. LINC00839 expression was up-regulated in liver cancer tissues and cell lines, and the patients with high LINC00839 expression had shortened overall survival. LINC00839 further overexpressed under hypoxia and promoted liver cancer cell proliferation, migration, and invasion. Mechanistically, LINC00839 bound multiple proteins that were primarily associated with the metabolism and RNA transport, and positively regulated the expression of Formin-like protein 2 (FMNL2). LINC00839 could promote hypoxia-mediated liver cancer progression, suggesting it may be a clinically valuable biomarker and serve as a molecular target for the diagnosis, prognosis, and therapy of liver cancer.

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References

Eales K, Hollinshead K, Tennant D . Hypoxia and metabolic adaptation of cancer cells. Oncogenesis. 2016; 5:e190. PMC: 4728679. DOI: 10.1038/oncsis.2015.50. View

Carnero A, Lleonart M . The hypoxic microenvironment: A determinant of cancer stem cell evolution. Bioessays. 2016; 38 Suppl 1:S65-74. DOI: 10.1002/bies.201670911. View

Packer L, Fuehr K . Low oxygen concentration extends the lifespan of cultured human diploid cells. Nature. 1977; 267(5610):423-5. DOI: 10.1038/267423a0. View

Mierke C . The matrix environmental and cell mechanical properties regulate cell migration and contribute to the invasive phenotype of cancer cells. Rep Prog Phys. 2019; 82(6):064602. DOI: 10.1088/1361-6633/ab1628. View

Jiao X, Wang B, Feng C, Song S, Tian B, Zhou C . Formin-like protein 2 promotes cell proliferation by a p27-related mechanism in human breast cancer cells. BMC Cancer. 2021; 21(1):760. PMC: 8247103. DOI: 10.1186/s12885-021-08533-w. View

Huarte M . The emerging role of lncRNAs in cancer. Nat Med. 2015; 21(11):1253-61. DOI: 10.1038/nm.3981. View

Chen Q, Shen H, Zhu X, Liu Y, Yang H, Chen H . A nuclear lncRNA Linc00839 as a Myc target to promote breast cancer chemoresistance via PI3K/AKT signaling pathway. Cancer Sci. 2020; 111(9):3279-3291. PMC: 7469761. DOI: 10.1111/cas.14555. View

McKeown S . Defining normoxia, physoxia and hypoxia in tumours-implications for treatment response. Br J Radiol. 2014; 87(1035):20130676. PMC: 4064601. DOI: 10.1259/bjr.20130676. View

Hangauer M, Vaughn I, McManus M . Pervasive transcription of the human genome produces thousands of previously unidentified long intergenic noncoding RNAs. PLoS Genet. 2013; 9(6):e1003569. PMC: 3688513. DOI: 10.1371/journal.pgen.1003569. View

10.

Ren X, Qiao Y, Li J, Li X, Zhang D, Zhang X . Cortactin recruits FMNL2 to promote actin polymerization and endosome motility in invadopodia formation. Cancer Lett. 2018; 419:245-256. DOI: 10.1016/j.canlet.2018.01.023. View

11.

Guo D, Xie K, Luo X . Hypoxia-induced elevated NDRG1 mediates apoptosis through reprograming mitochondrial fission in HCC. Gene. 2020; 741:144552. DOI: 10.1016/j.gene.2020.144552. View

12.

Llovet J, Montal R, Sia D, Finn R . Molecular therapies and precision medicine for hepatocellular carcinoma. Nat Rev Clin Oncol. 2018; 15(10):599-616. DOI: 10.1038/s41571-018-0073-4. View

13.

Lin X, Qiu B, Ma M, Zhang R, Hsu S, Liu H . Suppressing DRP1-mediated mitochondrial fission and mitophagy increases mitochondrial apoptosis of hepatocellular carcinoma cells in the setting of hypoxia. Oncogenesis. 2020; 9(7):67. PMC: 7359348. DOI: 10.1038/s41389-020-00251-5. View

14.

Vaupel P, Hockel M, Mayer A . Detection and characterization of tumor hypoxia using pO2 histography. Antioxid Redox Signal. 2007; 9(8):1221-35. DOI: 10.1089/ars.2007.1628. View

15.

Yang S, Li X, Yang M, Ren X, Hu J, Zhu X . FMNL2 destabilises COMMD10 to activate NF-κB pathway in invasion and metastasis of colorectal cancer. Br J Cancer. 2017; 117(8):1164-1175. PMC: 5674093. DOI: 10.1038/bjc.2017.260. View

16.

Seewaldt V . ECM stiffness paves the way for tumor cells. Nat Med. 2014; 20(4):332-3. DOI: 10.1038/nm.3523. View

17.

Ulitsky I, Bartel D . lincRNAs: genomics, evolution, and mechanisms. Cell. 2013; 154(1):26-46. PMC: 3924787. DOI: 10.1016/j.cell.2013.06.020. View

18.

Mattick J . The functional genomics of noncoding RNA. Science. 2005; 309(5740):1527-8. DOI: 10.1126/science.1117806. View

19.

Rankin E, Giaccia A . Hypoxic control of metastasis. Science. 2016; 352(6282):175-80. PMC: 4898055. DOI: 10.1126/science.aaf4405. View

20.

Ashburner M, Ball C, Blake J, Botstein D, Butler H, Cherry J . Gene ontology: tool for the unification of biology. The Gene Ontology Consortium. Nat Genet. 2000; 25(1):25-9. PMC: 3037419. DOI: 10.1038/75556. View