lncRNA FOXP4-AS1 predicts poor prognosis and accelerates the progression of mantle cell lymphoma through the miR-423-5p/NACC1 pathway
| Autor: | Hong‑Fang Tao, Yong‑Zhong Su, Zhan‑Wen Hou, Jia‑Xin Shen, Jian‑Lin Fang, Shao‑Yan Chen |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
Male
Cancer Research NACC1 Cell mantle cell lymphoma Lymphoma Mantle-Cell microR-423-5p Disease-Free Survival Downregulation and upregulation Cell Line Tumor medicine Humans Neoplasm Invasiveness FOXP4-AS1 Cell Proliferation Gene knockdown Oncogene Chemistry Cell growth Computational Biology General Medicine Articles Cell cycle Middle Aged Prognosis Molecular medicine Antisense RNA Neoplasm Proteins Up-Regulation Gene Expression Regulation Neoplastic Repressor Proteins MicroRNAs medicine.anatomical_structure Oncology Gene Knockdown Techniques Cancer research Disease Progression Female RNA Long Noncoding progression Neoplasm Recurrence Local Follow-Up Studies |
| Zdroj: | Oncology Reports |
| ISSN: | 1791-2431 1021-335X |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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