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Long noncoding RNA LINC01124 activates hepatocellular carcinoma cell proliferation, migration, and invasion by absorbing microRNA-1247-5p and overexpressing FOXO3

LEI SUN1,2, YUE ZHANG3, YUQIN YAO4, HONGLIN DU3, YUEHUA ZHANG1, AIPING FANG1,2,*

1 Department of Geriatric Medicine, West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, 610041, China
2 State Key Laboratory of Biotherapy/Collaborative Innovation Center for Biotherapy, West China Hospital, Sichuan University, Chengdu, 610041, China
3 Department of Hepatobiliary and Pancreas Surgery, Second Clinical Medical College of Jinan University (Shenzhen People’s Hospital), Shenzhen, China
4 Respiratory Disease Research Center, West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, 610041, China

* Corresponding Author: Aiping Fang, email

Oncology Research 2021, 29(3), 175-187. https://doi.org/10.32604/or.2022.03550

Abstract

Long intergenic non-protein coding RNA 1124 (LINC01124) has been identified as an important regulator of non-small-cell lung cancer. However, the expression and detailed role of LINC01124 in hepatocellular carcinoma (HCC) remain unestablished to date. Therefore, this study aimed to elucidate the role of LINC01124 in the aggressiveness of HCC cells and identify the underlying regulatory mechanism. Quantitative reverse transcriptase-polymerase chain reaction was performed to measure the expression of LINC01124 in HCC. Cell Counting Kit-8 assay, Transwell cell migration and invasion assays, and a xenograft tumor model were used to investigate the function of LINC01124 in HCC cells, and bioinformatics analysis, RNA immunoprecipitation, luciferase reporter assay, and rescue experiments were used to elucidate the underlying mechanisms. Herein, LINC01124 overexpression was confirmed in HCC tissues as well as cell lines. Further, the downregulation of LINC01124 decreased HCC cell proliferation, migration, and invasion in vitro, whereas the upregulation of LINC01124 triggered the opposite results. Additionally, LINC01124 ablation impaired tumor growth in vivo. Mechanistic analyses revealed that LINC01124 functions as a competing endogenous RNA to sponge microRNA-1247-5p (miR-1247-5p) in HCC cells. Moreover, forkhead box O3 (FOXO3) was identified as a direct target of miR-1247-5p. FOXO3 was positively regulated by LINC01124 in HCC cells through the sequestration of miR-1247-5p. Finally, rescue assays revealed that the inhibition of miR-1247-5p or overexpression of FOXO3 reversed the effects of LINC01124 silencing on the HCC cell malignant phenotype. In summary, LINC01124 plays a tumor-promoting role in HCC by regulating the miR-1247-5p–FOXO3 axis. The LINC01124–miR-1247-5p– FOXO3 pathway may provide a foundation for the identification of alternative therapies for HCC.

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APA Style
SUN, L., ZHANG, Y., YAO, Y., DU, H., ZHANG, Y. et al. (2021). Long noncoding RNA LINC01124 activates hepatocellular carcinoma cell proliferation, migration, and invasion by absorbing microrna-1247-5p and overexpressing FOXO3. Oncology Research, 29(3), 175-187. https://doi.org/10.32604/or.2022.03550
Vancouver Style
SUN L, ZHANG Y, YAO Y, DU H, ZHANG Y, FANG A. Long noncoding RNA LINC01124 activates hepatocellular carcinoma cell proliferation, migration, and invasion by absorbing microrna-1247-5p and overexpressing FOXO3. Oncol Res. 2021;29(3):175-187 https://doi.org/10.32604/or.2022.03550
IEEE Style
L. SUN, Y. ZHANG, Y. YAO, H. DU, Y. ZHANG, and A. FANG "Long noncoding RNA LINC01124 activates hepatocellular carcinoma cell proliferation, migration, and invasion by absorbing microRNA-1247-5p and overexpressing FOXO3," Oncol. Res., vol. 29, no. 3, pp. 175-187. 2021. https://doi.org/10.32604/or.2022.03550



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