Apatinib Inhibits Cell Proliferation and Migration of Osteosarcoma Via Activating LINC00261/miR-620/PTEN Axis

Overview

Journal Cell Cycle

Specialty Cell Biology

Date 2021 Aug 23

PMID 34424120

Citations 6

Authors

Gang Han

Quanyi Guo

Ning Ma

Wenzhi Bi

Meng Xu

Jinpeng Jia

Affiliations

Soon will be listed here.

Abstract

Apatinib has been recently identified as a potential treatment option for osteosarcoma (OS). Nonetheless, the molecular mechanism of Apatinib in regulating OS progression remains unclear. To explore the downstream molecules that mediated the tumor-suppressive effect of Apatinib on OS. Expression levels of genes were detected by RT-qPCR and western blot assays. Functional assays including Transwell assay were applied to detect the proliferation, apoptosis and migration of OS cells. Molecular interactions were detected by luciferase reporter assay and RIP assay. Apatinib inhibited the proliferation and migration of OS cells. LINC00261 was down-regulated in OS cells but then up-regulated after the treatment by Apatinib. Silencing LINC00261 abrogated the suppressive effect of Apatinib on OS cell proliferation and migration. MicroRNA-620 (miR-620) could be sponged by LINC00261. Besides, miR-620 was up-regulated in OS cells and Apatinib treatment reduced miR-620 expression. Furthermore, LINC00261 acted as a competitive endogenous RNA (ceRNA) by sequestering miR-620 to up-regulate the expression of phosphatase and tensin homolog (PTEN). Moreover, Apatinib hindered cell proliferation and migration as well as the tumorigenesis of OS through LINC00261/miR-620/PTEN axis. Apatinib-enhanced LINC00261 restrained OS via miR-620/PTEN axis, indicating LINC00261 might promote the efficacy of Apatinib on OS.

Citing Articles

The combination of apatinib and antigen-specific DC-induced T cells exert antitumor effects by potently improving the immune microenvironment of osteosarcoma.

Hu T, Sun W, Jin Y, Dong Y, Liu W, Sun Z Heliyon. 2024; 10(16):e36016.

PMID: 39224314 PMC: 11367533. DOI: 10.1016/j.heliyon.2024.e36016.

Osteosarcoma in a ceRNET perspective.

Mosca N, Alessio N, Di Paola A, Marrapodi M, Galderisi U, Russo A J Biomed Sci. 2024; 31(1):59.

PMID: 38835012 PMC: 11151680. DOI: 10.1186/s12929-024-01049-y.

Apatinib plus chemotherapy for non-metastatic osteosarcoma: a retrospective cohort study.

Wang J, Zhang F, Dong S, Yang Y, Gao F, Liu G Front Oncol. 2023; 13:1227461.

PMID: 38023239 PMC: 10679406. DOI: 10.3389/fonc.2023.1227461.

Rintatolimod: a potential treatment in patients with pancreatic cancer expressing Toll-like receptor 3.

Haddaoui H, van Eijck C, Doukas M, van den Bosch T, Van Koetsveld P, Hofland L Am J Cancer Res. 2023; 13(6):2657-2669.

PMID: 37424830 PMC: 10326577.

Functional role of MicroRNA/PI3K/AKT axis in osteosarcoma.

Xiang Y, Yang Y, Liu J, Yang X Front Oncol. 2023; 13:1219211.

PMID: 37404761 PMC: 10315918. DOI: 10.3389/fonc.2023.1219211.

References

Li L, Yin J, He F, Huang M, Zhu T, Gao Y . Long noncoding RNA promoted apoptosis and increased cisplatin chemosensitivity via regulating the hnRNP-U-GADD45A axis in lung squamous cell carcinoma. Oncotarget. 2017; 8(57):97476-97489. PMC: 5722577. DOI: 10.18632/oncotarget.22138. View

Chen C, Zhou L, Wang H, Chen J, Li W, Liu W . Long noncoding RNA CNALPTC1 promotes cell proliferation and migration of papillary thyroid cancer via sponging miR-30 family. Am J Cancer Res. 2018; 8(1):192-206. PMC: 5794733. View

Anderson M . Update on Survival in Osteosarcoma. Orthop Clin North Am. 2015; 47(1):283-92. DOI: 10.1016/j.ocl.2015.08.022. View

Wang Z, Liu Z, Wu S . Long non-coding RNA CTA sensitizes osteosarcoma cells to doxorubicin through inhibition of autophagy. Oncotarget. 2017; 8(19):31465-31477. PMC: 5458222. DOI: 10.18632/oncotarget.16356. View

Tabellini G, Cappellini A, Tazzari P, Fala F, Billi A, Manzoli L . Phosphoinositide 3-kinase/Akt involvement in arsenic trioxide resistance of human leukemia cells. J Cell Physiol. 2004; 202(2):623-34. DOI: 10.1002/jcp.20153. View

E C, Yang J, Li H, Li C . LncRNA LOC105372579 promotes proliferation and epithelial-mesenchymal transition in hepatocellular carcinoma via activating miR-4316/FOXP4 signaling. Cancer Manag Res. 2019; 11:2871-2879. PMC: 6489618. DOI: 10.2147/CMAR.S197979. View

Lei W, Wang Z, Feng H, Lin X, Li C, Fan D . Long non-coding RNA SNHG12promotes the proliferation and migration of glioma cells by binding to HuR. Int J Oncol. 2018; 53(3):1374-1384. DOI: 10.3892/ijo.2018.4478. View

Chen D, Lu Y, Zhang J, Wei X, Wang F, Zeng Z . Long non-coding RNA UICLM promotes colorectal cancer liver metastasis by acting as a ceRNA for microRNA-215 to regulate ZEB2 expression. Theranostics. 2017; 7(19):4836-4849. PMC: 5706103. DOI: 10.7150/thno.20942. View

Hu X, Zhang J, Xu B, Jiang Z, Ragaz J, Tong Z . Multicenter phase II study of apatinib, a novel VEGFR inhibitor in heavily pretreated patients with metastatic triple-negative breast cancer. Int J Cancer. 2014; 135(8):1961-9. DOI: 10.1002/ijc.28829. View

10.

Zhou M, Gu L, Findley H, Jiang R, Woods W . PTEN reverses MDM2-mediated chemotherapy resistance by interacting with p53 in acute lymphoblastic leukemia cells. Cancer Res. 2003; 63(19):6357-62. View

11.

Zhuang M, Qiu X, Cheng D, Zhu C, Chen L . MicroRNA-524 promotes cell proliferation by down-regulating PTEN expression in osteosarcoma. Cancer Cell Int. 2018; 18:114. PMC: 6090628. DOI: 10.1186/s12935-018-0612-1. View

12.

Wang Z, Yang L, Wu L, Mao H, Zhou Y, Zhang P . Long non-coding RNA LINC00261 sensitizes human colon cancer cells to cisplatin therapy. Braz J Med Biol Res. 2017; 51(2):e6793. PMC: 5731330. DOI: 10.1590/1414-431X20176793. View

13.

Livak K, Schmittgen T . Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods. 2002; 25(4):402-8. DOI: 10.1006/meth.2001.1262. View

14.

Sha L, Huang L, Luo X, Bao J, Gao L, Pan Q . Long non-coding RNA LINC00261 inhibits cell growth and migration in endometriosis. J Obstet Gynaecol Res. 2017; 43(10):1563-1569. DOI: 10.1111/jog.13427. View

15.

Liu K, Ren T, Huang Y, Sun K, Bao X, Wang S . Apatinib promotes autophagy and apoptosis through VEGFR2/STAT3/BCL-2 signaling in osteosarcoma. Cell Death Dis. 2017; 8(8):e3015. PMC: 5596600. DOI: 10.1038/cddis.2017.422. View

16.

Zhao Z, Han C, Liu J, Wang C, Wang Y, Cheng L . GPC5, a tumor suppressor, is regulated by miR-620 in lung adenocarcinoma. Mol Med Rep. 2014; 9(6):2540-6. DOI: 10.3892/mmr.2014.2092. View

17.

Li J, Qin S, Xu J, Guo W, Xiong J, Bai Y . Apatinib for chemotherapy-refractory advanced metastatic gastric cancer: results from a randomized, placebo-controlled, parallel-arm, phase II trial. J Clin Oncol. 2013; 31(26):3219-25. DOI: 10.1200/JCO.2013.48.8585. View

18.

Hu X, Li L, Lu Y, Yu X, Chen H, Yin Q . miRNA-21 inhibition inhibits osteosarcoma cell proliferation by targeting PTEN and regulating the TGF-β1 signaling pathway. Oncol Lett. 2018; 16(4):4337-4342. PMC: 6144926. DOI: 10.3892/ol.2018.9177. View

19.

Peng H, Zhang Q, Li J, Zhang N, Hua Y, Xu L . Apatinib inhibits VEGF signaling and promotes apoptosis in intrahepatic cholangiocarcinoma. Oncotarget. 2016; 7(13):17220-9. PMC: 4941382. DOI: 10.18632/oncotarget.7948. View

20.

Wang Y, Xue K, Guan Y, Jin Y, Liu S, Wang Y . Long Noncoding RNA LINC00261 Suppresses Cell Proliferation and Invasion and Promotes Cell Apoptosis in Human Choriocarcinoma. Oncol Res. 2016; 25(5):733-742. PMC: 7841083. DOI: 10.3727/096504016X14772362173376. View