Downregulation of lncRNA FOXD2-AS1 Confers Radiosensitivity to Gastric Cancer Cells via miR-1913/SETD1A Axis

Cytogenetic and Genome Research

Guo F.a· Guo R.a· Zhang L.b

Author affiliations

aDepartment of Tumor Radiotherapy, Zhongshan Hospital Xiamen University, Xiamen, China
bDepartment of Anesthesia Resuscitation Room, Zhongshan Hospital Xiamen University, Xiamen, China

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Article / Publication Details

First-Page Preview

Abstract of Original Article

Received: October 26, 2021
Accepted: February 14, 2022
Published online: March 30, 2022

Number of Print Pages: 18
Number of Figures: 6
Number of Tables: 0

ISSN: 1424-8581 (Print)
eISSN: 1424-859X (Online)

For additional information: https://www.karger.com/CGR

Abstract

Long noncoding RNA FOXD2 adjacent opposite strand RNA1 (FOXD2-AS1) plays an oncogenic role in various cancers, including gastric cancer (GC). However, the function of FOXD2-AS1 in regulating radiosensitivity of GC cells and its underlying molecular mechanisms have not been elucidated. This study aimed to figure out the potential mechanisms of FOXD2-AS1 in regulating GC cell radiosensitivity. RT-qPCR revealed upregulation of FOXD2-AS1 in GC cells exposed to radiation. Subcellular fractionation assay was used to localize FOXD2-AS1 in GC cells. Colony formation, MTT, EdU, and flow cytometry assays were performed to investigate the role of FOXD2-AS1 in regulating cell proliferation, cell cycle progression, and cell apoptosis. Western blotting was used to assess protein levels of apoptosis-associated markers and SET domain containing 1A (SETD1A). Homologous recombination reporter assay was conducted to explore the effect of FOXD2-AS1 on DNA damage repair. The downstream molecules of FOXD2-AS1 were identified with RNA pulldown, luciferase reporter, and RNA immunoprecipitation assays. The results showed that FOXD2-AS1 knockdown suppressed cell proliferation and cell cycle progression and promoted cell apoptosis and radiosensitivity of GC. FOXD2-AS1 could bind with miR-1913 in GC cells. In addition, miR-1913 targeted SETD1A, which was highly expressed in GC cells. Overexpression of SETD1A reversed FOXD2-AS1 silencing-induced effects on proliferation, apoptosis, and radiosensitivity of GC cells. In conclusion, knocking down FOXD2-AS1 enhances the radiosensitivity of GC cells by sponging miR-1913 to upregulate SETD1A expression.

© 2022 S. Karger AG, Basel

References Alshahrani S, Baabbad F, Bahobail M, Hawsawi A, Jastania E, Bamousa S, et al. Survival Time in Treatment Modalities of Gastric Carcinoma at King Khalid Hospital - Jeddah Saudi Arabia: a Retrospective Cohort Study. Mater Sociomed. 2020;32:271–6. Arnold M, Park JY, Camargo MC, Lunet N, Forman D, Soerjomataram I. Is gastric cancer becoming a rare disease? A global assessment of predicted incidence trends to 2035. Gut. 2020;69:823–9. Atianand MK, Caffrey DR, Fitzgerald KA. Immunobiology of Long Noncoding RNAs. Annu Rev Immunol. 2017;35:177–98. Bai Y, Long J, Liu Z, Lin J, Huang H, Wang D, et al. Comprehensive analysis of a ceRNA network reveals potential prognostic cytoplasmic lncRNAs involved in HCC progression. J Cell Physiol. 2019;234:18837–48. Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018;68:394–424. Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Erratum. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2020;70:313. Chen J, Feng J, Fang Z, Ye J, Chen Q, Chen Q, et al. Anlotinib suppresses MLL-rearranged acute myeloid leukemia cell growth by inhibiting SETD1A/AKT-mediated DNA damage response. Am J Transl Res. 2021;13(3):1494–504. Dou X, Zhou Q, Wen M, Xu J, Zhu Y, Zhang S, et al. Long Noncoding RNA FOXD2-AS1 Promotes the Malignancy of Cervical Cancer by Sponging MicroRNA-760 and Upregulating Hepatoma-Derived Growth Factor. Front Pharmacol. 2019;10:1700. Gantuya B, Oyuntsetseg K, Bolor D, Erdene-Ochir Y, Sanduijav R, Davaadorj D, et al. Evaluation of serum markers for gastric cancer and its precursor diseases among high incidence and mortality rate of gastric cancer area. Gastric Cancer. 2019;22:104–12. Gao J, Liu F, Zhao X, Zhang P. Long non-coding RNA FOXD2-AS1 promotes proliferation, migration and invasion of ovarian cancer cells via regulating the expression of miR-4492. Exp Ther Med. 2021;21(4):307. Han F, Yang S, Wang W, Huang X, Huang D, Chen S. Silencing of lncRNA LINC00857 Enhances BIRC5-Dependent Radio-Sensitivity of Lung Adenocarcinoma Cells by Recruiting NF-κB1. Mol Ther Nucleic Acids. 2020;22:981–93. Hoshii T, Cifani P, Feng Z, Huang CH, Koche R, Chen CW, et al. A Non-catalytic Function of SETD1A Regulates Cyclin K and the DNA Damage Response. Cell. 2018;172:1007–21.e17. Hu Q, Tai S, Wang J. Oncogenicity of lncRNA FOXD2-AS1 and its molecular mechanisms in human cancers. Pathol Res Pract. 2019;215:843–8. Hu YP, Jin YP, Wu XS, Yang Y, Li YS, Li HF, et al. LncRNA-HGBC stabilized by HuR promotes gallbladder cancer progression by regulating miR-502-3p/SET/AKT axis. Mol Cancer. 2019;18:167. Ji F, Sha H, Meng F, Zhu A, Ding N, Zhang H, et al. [Corrigendum] Tumorpenetrating peptide fused EGFR singledomain antibody enhances radiation responses following EGFR inhibition in gastric cancer. Oncol Rep. 2021;45(1):404–5. Jiang Y, Jin S, Tan S, Xue Y, Cao X. Long noncoding RNA NEAT1 regulates radio-sensitivity via microRNA-27b-3p in gastric cancer. Cancer Cell Int. 2020;20:581. Li S, Jia H, Zhang Z, Wu D. LncRNA GAS6-AS1 facilitates the progression of breast cancer by targeting the miR-324-3p/SETD1A axis to activate the PI3K/AKT pathway. Eur J Cell Biol. 2020;99:151124. Liu M, Chen H, Chen X, Xiong J, Song Z. Silencing UCHL3 enhances radio-sensitivity of non-small cell lung cancer cells by inhibiting DNA repair. Aging (Albany NY). 2021;13(10):14277–88. Liu Z, Zhou W, Lin C, Wang X, Zhang X, Zhang Y, et al. Dysregulation of FOXD2-AS1 promotes cell proliferation and migration and predicts poor prognosis in oral squamous cell carcinoma: a study based on TCGA data. Aging (Albany NY). 2020;13(2):2379–96. Ma C, Wang X, Yang F, Zang Y, Liu J, Wang X, et al. Circular RNA hsa_circ_0004872 inhibits gastric cancer progression via the miR-224/Smad4/ADAR1 successive regulatory circuit. Mol Cancer. 2020;19:157. Malinowska AL, Laski A, Hall J. Design and application of mini‐libraries of miRNA probes for an efficient and versatile miRNA‐mRNA cross‐linking. Chem Eur J. 2021;27(39):10193–200. O'Leary BR, Houwen FK, Johnson CL, Allen BG, Mezhir JJ, Berg DJ, et al. Pharmacological Ascorbate as an Adjuvant for Enhancing Radiation-Chemotherapy Responses in Gastric Adenocarcinoma. Radiat Res. 2018;189:456–65. Renganathan A, Felley-Bosco E. Long Noncoding RNAs in Cancer and Therapeutic Potential. Adv Exp Med Biol. 2017;1008:199–222. Salmena L, Poliseno L, Tay Y, Kats L, Pandolfi PP. A ceRNA hypothesis: the Rosetta Stone of a hidden RNA language? Cell. 2011;146:353–8. Ståhlberg A, Kubista M, Pfaffl M. Comparison of reverse transcriptases in gene expression analysis. Clin Chem. 2004;50:1678–80. Statello L, Guo CJ, Chen LL, Huarte M. Gene regulation by long non-coding RNAs and its biological functions. Nat Rev Mol Cell Biol. 2021;22(2):96–118. Taniue K, Akimitsu N. The Functions and Unique Features of lncRNAs in Cancer Development and Tumorigenesis. Int J Mol Sci. 2021;22(2):632. Tian Y, Ma R, Sun Y, Liu H, Zhang H, Sun Y, et al. Correction: SP1-activated long noncoding RNA lncRNA GCMA functions as a competing endogenous RNA to promote tumor metastasis by sponging miR-124 and miR-34a in gastric cancer. Oncogene. 2020;39:6621. Wagner AD, Grothe W, Haerting J, Kleber G, Grothey A, Fleig WE. Chemotherapy in advanced gastric cancer: a systematic review and meta-analysis based on aggregate data. J Clin Oncol. 2006;24:2903–9. Wang YP, Li HQ, Chen JX, Kong FG, Mo ZH, Wang JZ, et al. Overexpression of XIST facilitates cell proliferation, invasion and suppresses cell apoptosis by reducing radio-sensitivity of glioma cells via miR-329-3p/CREB1 axis. Eur Rev Med Pharmacol Sci. 2020;24:3190–203. Wu J, Chai H, Xu X, Yu J, Gu Y. Histone methyltransferase SETD1A interacts with HIF1α to enhance glycolysis and promote cancer progression in gastric cancer. Mol Oncol. 2020;14:1397–409. Wu Z, Qiu M, Guo Y, Zhao J, Liu Z, Wang H, et al. OTU deubiquitinase 4 is silenced and radiosensitizes non-small cell lung cancer cells via inhibiting DNA repair. Cancer Cell Int. 2019;19:99. Xu J, Meng Q, Li X, Yang H, Xu J, Gao N, et al. Long Noncoding RNA MIR17HG Promotes Colorectal Cancer Progression via miR-17-5p. Cancer Res. 2019;79:4882–95. Xu J, Zhao L, Peng S, Chu H, Liang R, Tian M, et al. Mechanisms of distinctive mismatch tolerance between Rad51 and Dmc1 in homologous recombination. Nucleic Acids Res. 2021;49(22):13135–49. Xu TP, Wang WY, Ma P, Shuai Y, Zhao K, Wang YF, et al. Upregulation of the long noncoding RNA FOXD2-AS1 promotes carcinogenesis by epigenetically silencing EphB3 through EZH2 and LSD1, and predicts poor prognosis in gastric cancer. Oncogene. 2018;37:5020–36. Yang QS, Li B, Xu G, Yang SQ, Wang P, Tang HH, et al. Long noncoding RNA LINC00483/microRNA-144 regulates radiosensitivity and epithelial-mesenchymal transition in lung adenocarcinoma by interacting with HOXA10. J Cell Physiol. 2019;234:11805–21. Zhang JK, Fang LL, Zhang DW, Jin Q, Wu XM, Liu JC, et al. Type D Personality in Gastric Cancer Survivors: Association With Poor Quality of Life, Overall Survival, and Mental Health. J Pain Symptom Manage. 2016;52:81–91. Zhang M, Jiang X, Jiang S, Guo Z, Zhou Q, He J. LncRNA FOXD2-AS1 Regulates miR-25-3p/Sema4c Axis To Promote The Invasion And Migration Of Colorectal Cancer Cells. Cancer Manag Res. 2019;11:10633–9. Zhao J, Zeng X-B, Zhang H-Y, Xiang J-W, Liu Y-S. Long non-coding RNA FOXD2-AS1 promotes cell proliferation, metastasis and EMT in glioma by sponging miR-506-5p. Open Med (Wars). 2020;15(1):921–31. Zhao T, Zhang J, Ye C, Tian L, Li Y. lncRNA FOXD2-AS1 promotes hemangioma progression through the miR-324-3p/PDRG1 pathway. Cancer Cell Int. 2020;20:189. Zhou J, Wu X, Li G, Gao X, Zhai M, Chen W, et al. Prediction of radiosensitive patients with gastric cancer by developing gene signature. Int J Oncol. 2017;51:1067–76. Zhou M, Wang H, Zeng X, Yin P, Zhu J, Chen W, et al. Mortality, morbidity, and risk factors in China and its provinces, 1990-2017: a systematic analysis for the Global Burden of Disease Study 2017. Lancet. 2019;394:1145–58. Zhou Q, Huang XR, Yu J, Yu X, Lan HY. Long Noncoding RNA Arid2-IR Is a Novel Therapeutic Target for Renal Inflammation. Mol Ther. 2015;23:1034–43. Article / Publication Details

First-Page Preview

Abstract of Original Article

Received: October 26, 2021
Accepted: February 14, 2022
Published online: March 30, 2022

Number of Print Pages: 18
Number of Figures: 6
Number of Tables: 0

ISSN: 1424-8581 (Print)
eISSN: 1424-859X (Online)

For additional information: https://www.karger.com/CGR

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