lncRNA FOXP4‑AS1 predicts poor prognosis and accelerates the progression of mantle cell lymphoma through the miR‑423‑5p/NACC1 pathway

Tao,Hong‑Fang; Shen,Jia‑Xin; Hou,Zhan‑Wen; Chen,Shao‑Yan; Su,Yong‑Zhong; Fang,Jian‑Lin

doi:10.3892/or.2020.7897

lncRNA FOXP4‑AS1 predicts poor prognosis and accelerates the progression of mantle cell lymphoma through the miR‑423‑5p/NACC1 pathway

Authors:
- Hong‑Fang Tao
- Jia‑Xin Shen
- Zhan‑Wen Hou
- Shao‑Yan Chen
- Yong‑Zhong Su
- Jian‑Lin Fang
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Affiliations: Department of Hematology, The First Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong 515041, P.R. China, Department of Intervention Therapy, The First Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong 515041, P.R. China
Published online on: December 11, 2020 https://doi.org/10.3892/or.2020.7897
Pages: 469-480
Copyright: © Tao et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Long non‑coding RNA (lncRNA) forkhead box P4 antisense RNA 1 (FOXP4‑AS1) has been determined to function as an oncogene in various types of cancer. However, the biological function and the underlying mechanisms of FOXP4‑AS1 in mantle cell lymphoma (MCL) remain to be uncovered. The expression and the associated clinicopathological characteristics and prognostic significance of FOXP4‑AS1 were explored in MCL clinical samples. The effects of FOXP4‑AS1 on MCL cellular behaviors, including proliferation, migration and invasion were analyzed using CCK‑8, crystal violet and Transwell assays. The downstream molecules of FOXP4‑AS1 were explored using bioinformatics analysis and dual luciferase assay. Our results showed that FOXP4‑AS1 expression was upregulated in MCL patients, and that the high expression of FOXP4‑AS1 was correlated with the unfavorable prognosis of patients. Functionally, while FOXP4‑AS1 downregulation inhibited proliferation, migration and invasion of MCL cells, FOXP4‑AS1 overexpression had promotive effects on these cellular processes. Mechanistically, FOXP4‑AS1 was found to act as a competing endogenous (ce)RNA for miR‑423‑5p to regulate the expression of nucleus accumbens‑associated 1 (NACC1). The negative regulation of FOXP4‑AS1 on miR‑423‑5p compared to that of miR‑423‑5p on NACC1 was determined at the mRNA or protein levels in MCL cells. Moreover, an inverse expression correlation between FOXP4‑AS1 and miR‑423‑5p, and that between miR‑423‑5p and NACC1 was confirmed in MCL clinical samples. In addition, rescue assay showed that miR‑423‑5p upregulation or NACC1 knockdown abolished the promoting effects of FOXP4‑AS1 on MCL cell proliferation, migration and invasion. In conclusion, FOXP4‑AS1 promotes MCL progression through the upregulation of NACC1 expression by inhibiting miR‑423‑5p. FOXP4‑AS1 may serve as a novel therapeutic target for patients with MCL.

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1	Vose JM: Mantle cell lymphoma: 2017 update on diagnosis, risk-stratification, and clinical management. Am J Hematol. 92:806–813. 2017. View Article : Google Scholar : PubMed/NCBI
2	Eskelund CW, Kolstad A, Jerkeman M, Räty R, Laurell A, Eloranta S, Smedby KE, Husby S, Pedersen LB, Andersen NS, et al: 15-Year follow-up of the second nordic mantle cell lymphoma trial (MCL2): Prolonged remissions without survival plateau. Br J Haematol. 175:410–418. 2016. View Article : Google Scholar : PubMed/NCBI
3	Chihara D, Asano N, Ohmachi K, Kinoshita T, Okamoto M, Maeda Y, Mizuno I, Matsue K, Uchida T, Nagai H, et al: Prognostic model for mantle cell lymphoma in the rituximab era: A nationwide study in Japan. Br J Haematol. 170:657–668. 2015. View Article : Google Scholar : PubMed/NCBI
4	Dreyling M, Amador V, Callanan M, Jerkeman M, Le Gouill S, Pott C, Rule S and Zaja F; European Mantle Cell Lymphoma Network, : Update on the molecular pathogenesis and targeted approaches of mantle cell lymphoma: Summary of the 12th annual conference of the European mantle cell lymphoma network. Leuk Lymphoma. 56:866–876. 2015. View Article : Google Scholar : PubMed/NCBI
5	Prensner JR and Chinnaiyan AM: The emergence of lncRNAs in cancer biology. Cancer Discov. 1:391–407. 2011. View Article : Google Scholar : PubMed/NCBI
6	Wapinski O and Chang HY: Long noncoding RNAs and human disease. Trends Cell Biol. 21:354–361. 2011. View Article : Google Scholar : PubMed/NCBI
7	Wang X, Sehgal L, Jain N, Khashab T, Mathur R and Samaniego F: LncRNA MALAT1 promotes development of mantle cell lymphoma by associating with EZH2. J Transl Med. 14:3462016. View Article : Google Scholar : PubMed/NCBI
8	Mu G, Liu Q, Wu S, Xia Y and Fang Q: Long noncoding RNA HAGLROS promotes the process of mantle cell lymphoma by regulating miR-100/ATG5 axis and involving in PI3K/AKT/mTOR signal. Artif Cells Nanomed Biotechnol. 47:3649–3656. 2019. View Article : Google Scholar : PubMed/NCBI
9	Fan Z, Wang X, Li P, Mei C, Zhang M and Zhao C: Overexpression of lncRNA GATA6-AS inhibits cancer cell proliferation in mantle cell lymphoma by downregulating GLUT1. Oncol Lett. 18:2443–2447. 2019.PubMed/NCBI
10	Qu L, Ding J, Chen C, Wu ZJ, Liu B, Gao Y, Chen W, Liu F, Sun W, Li XF, et al: Exosome-transmitted lncARSR promotes sunitinib resistance in renal cancer by acting as a competing endogenous RNA. Cancer Cell. 29:653–668. 2016. View Article : Google Scholar : PubMed/NCBI
11	Yang L, Ge D, Chen X, Qiu J, Yin Z, Zheng S and Jiang C: FOXP4-AS1 participates in the development and progression of osteosarcoma by downregulating LATS1 via binding to LSD1 and EZH2. Biochem Biophys Res Commun. 502:493–500. 2018. View Article : Google Scholar : PubMed/NCBI
12	Wu X, Xiao Y, Zhou Y, Zhou Z and Yan W: LncRNA FOXP4-AS1 is activated by PAX5 and promotes the growth of prostate cancer by sequestering miR-3184-5p to upregulate FOXP4. Cell Death Dis. 10:4722019. View Article : Google Scholar : PubMed/NCBI
13	Li J, Lian Y, Yan C, Cai Z, Ding J, Ma Z, Peng P and Wang K: Long non-coding RNA FOXP4-AS1 is an unfavourable prognostic factor and regulates proliferation and apoptosis in colorectal cancer. Cell Prolif. 50:e123122017. View Article : Google Scholar
14	Li Y, Li T, Yang Y, Kang W, Dong S and Cheng S: YY1-Induced upregulation of FOXP4-AS1 and FOXP4 promote the proliferation of esophageal squamous cell carcinoma cells. Cell Biol Int. 44:1447–1457. 2020. View Article : Google Scholar : PubMed/NCBI
15	Zhao J, Yang T and Li L: LncRNA FOXP4-AS1 is involved in cervical cancer progression via regulating miR-136-5p/CBX4 axis. Onco Targets Ther. 13:2347–2355. 2020. View Article : Google Scholar : PubMed/NCBI
16	Faiola F, Yin N, Fidalgo M, Huang X, Saunders A, Ding J, Guallar D, Dang B and Wang J: NAC1 regulates somatic cell reprogramming by controlling Zeb1 and E-cadherin expression. Stem Cell Reports. 9:913–926. 2017. View Article : Google Scholar : PubMed/NCBI
17	Ju T, Jin H, Ying R, Xie Q, Zhou C and Gao D: Overexpression of NAC1 confers drug resistance via HOXA9 in colorectal carcinoma cells. Mol Med Rep. 16:3194–3200. 2017. View Article : Google Scholar : PubMed/NCBI
18	Nakayama N, Kato H, Sakashita G, Nariai Y, Nakayama K, Kyo S and Urano T: Protein complex formation and intranuclear dynamics of NAC1 in cancer cells. Arch Biochem Biophys. 606:10–15. 2016. View Article : Google Scholar : PubMed/NCBI
19	Fujii T, Shimada K, Tatsumi Y, Tanaka N, Fujimoto K and Konishi N: Syndecan-1 up-regulates microRNA-331-3p and mediates epithelial-to-mesenchymal transition in prostate cancer. Mol Carcinog. 55:1378–1386. 2016. View Article : Google Scholar : PubMed/NCBI
20	Rahman MT, Nakayama K, Rahman M, Katagiri H, Katagiri A, Ishibashi T, Ishikawa M, Iida K, Nakayama N, Otsuki Y, et al: Fatty acid synthase expression associated with NAC1 is a potential therapeutic target in ovarian clear cell carcinomas. Br J Cancer. 107:300–307. 2012. View Article : Google Scholar : PubMed/NCBI
21	Tatemichi Y, Shibazaki M, Yasuhira S, Kasai S, Tada H, Oikawa H, Suzuki Y, Takikawa Y, Masuda T and Maesawa C: Nucleus accumbens associated 1 is recruited within the promyelocytic leukemia nuclear body through SUMO modification. Cancer Sci. 106:848–856. 2015. View Article : Google Scholar : PubMed/NCBI
22	Sollier E, Cubizolles M, Fouillet Y and Achard JL: Fast and continuous plasma extraction from whole human blood based on expanding cell-free layer devices. Biomed Microdevices. 12:485–497. 2010. View Article : Google Scholar : PubMed/NCBI
23	Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods. 25:402–408. 2001. View Article : Google Scholar : PubMed/NCBI
24	Cao C, Zhang T, Zhang D, Xie L, Zou X, Lei L, Wu D and Liu L: The long non-coding RNA, SNHG6-003, functions as a competing endogenous RNA to promote the progression of hepatocellular carcinoma. Oncogene. 36:1112–1122. 2017. View Article : Google Scholar : PubMed/NCBI
25	Lin H, Lin T, Lin J, Yang M, Shen Z, Liu H, Zou Z and Zheng Z: Inhibition of miR-423-5p suppressed prostate cancer through targeting GRIM-19. Gene. 688:93–97. 2019. View Article : Google Scholar : PubMed/NCBI
26	Tang X, Zeng X, Huang Y, Chen S, Lin F, Yang G and Yang N: MiR-423-5p serves as a diagnostic indicator and inhibits the proliferation and invasion of ovarian cancer. Exp Ther Med. 15:4723–4730. 2018.PubMed/NCBI
27	Wang X, Peng L, Gong X, Zhang X, Sun R and Du J: MiR-423-5p inhibits osteosarcoma proliferation and invasion through directly targeting STMN1. Cell Physiol Biochem. 50:2249–2259. 2018. View Article : Google Scholar : PubMed/NCBI
28	Fang Z, Tang J, Bai Y, Lin H, You H, Jin H, Lin L, You P, Li J, Dai Z, et al: Plasma levels of microRNA-24, microRNA-320a, and microRNA-423-5p are potential biomarkers for colorectal carcinoma. J Exp Clin Cancer Res. 34:862015. View Article : Google Scholar : PubMed/NCBI
29	Vanacore D, Boccellino M, Rossetti S, Cavaliere C, D'Aniello C, Di Franco R, Romano FJ, Montanari M, La Mantia E, Piscitelli R, et al: Micrornas in prostate cancer: An overview. Oncotarget. 8:50240–50251. 2017. View Article : Google Scholar : PubMed/NCBI
30	Jiang C, Chen X, Alattar M, Wei J and Liu H: MicroRNAs in tumorigenesis, metastasis, diagnosis and prognosis of gastric cancer. Cancer Gene Ther. 22:291–301. 2015. View Article : Google Scholar : PubMed/NCBI
31	Nana-Sinkam SP and Croce CM: MicroRNA regulation of tumorigenesis, cancer progression and interpatient heterogeneity: Towards clinical use. Genome Biol. 15:4452014. View Article : Google Scholar : PubMed/NCBI