Long Non-Coding RNA BLACAT1 Promotes the Tumorigenesis of Gastric Cancer by Sponging MicroRNA-149-5p and Targeting KIF2A

Overview

Journal Cancer Manag Res

Publisher Dove Medical Press

Specialty Oncology

Date 2020 Aug 18

PMID 32801897

Citations 8

Authors

Zhengkun Wang

Xichun Liu

Xiaolei Liu

Dongguang Niu

Affiliations

Soon will be listed here.

Abstract

Objective: Gastric cancer (GC) is a gastrointestinal tumor. This study is aimed to explore the regulatory mechanism of long non-coding RNA BLACAT1 (BLACAT1)/microRNA-149-5p (miR-149-5p)/KIF2A cascade on GC.

Methods: The expression of BLACAT1, miR-149-5p and KIF2A in GC was detected by qRT-PCR. The proliferation, migration and invasion of GC cells in vitro were analyzed by MTT, wound-healing and transwell assay, respectively. The xenograft tumor model was constructed in nude mice to confirm the inhibition effect of BLACAT1 knockdown on GC in vivo. Then, dual-luciferase reporter assay was used to detect the interactions among BLACAT1, miR-149-5p and KIF2A. Western blot assay was performed to determine the protein expression of KIF2A.

Results: The expression of BLACAT1 and KIF2A was up-regulated in GC, but miR-149-5p expression was down-regulated. Silencing of BLACAT1 retarded the proliferation, migration and invasion of GC cells in vitro and the growth of tumor xenograft in vivo. Moreover, BLACAT1 acted as the molecular sponge of miR-149-5p to up-regulate KIF2A expression. At last, feedback experiments suggested that BLACAT1 accelerated the proliferation, migration and invasion of GC cells by regulating miR-149-5p/KIF2A axis.

Conclusion: BLACAT1 facilitated the tumorigenesis of GC through regulating miR-149-5p/KIF2A axis, which indicated BLACAT1/miR-149-5p/KIF2A cascade may be a new therapeutic target.

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References

Zhang Y, You X, Liu H, Xu M, Dang Q, Yang L . High KIF2A expression predicts unfavorable prognosis in diffuse large B cell lymphoma. Ann Hematol. 2017; 96(9):1485-1491. PMC: 5537331. DOI: 10.1007/s00277-017-3047-1. View

Yang H, Qi Y, Wang X, Gu J, Shi T . Down-regulation of lncRNA BLACAT1 inhibits ovarian cancer progression by suppressing the Wnt/β-catenin signaling pathway via regulating miR-519d-3p. Mol Cell Biochem. 2020; 467(1-2):95-105. DOI: 10.1007/s11010-020-03704-y. View

Xie T, Li X, Ye F, Lu C, Huang H, Wang F . High KIF2A expression promotes proliferation, migration and predicts poor prognosis in lung adenocarcinoma. Biochem Biophys Res Commun. 2018; 497(1):65-72. DOI: 10.1016/j.bbrc.2018.02.020. View

Huang Y, Zhang J, Hou L, Wang G, Liu H, Zhang R . LncRNA AK023391 promotes tumorigenesis and invasion of gastric cancer through activation of the PI3K/Akt signaling pathway. J Exp Clin Cancer Res. 2017; 36(1):194. PMC: 5745957. DOI: 10.1186/s13046-017-0666-2. View

Uchida A, Seki N, Mizuno K, Yamada Y, Misono S, Sanada H . Regulation of by Antitumor Inhibits Cancer Cell Aggressiveness Features in Lung Squamous Cell Carcinoma. Cancers (Basel). 2019; 11(2). PMC: 6406917. DOI: 10.3390/cancers11020258. View

Figueiredo C, Costa S, Karameris A, Machado J . Pathogenesis of Gastric Cancer. Helicobacter. 2015; 20 Suppl 1:30-5. DOI: 10.1111/hel.12254. View

Li X, Qi S, Ma D, Fan J, Wang J . Long non-coding RNA BLACAT1 promotes the proliferation and invasion of glioma cells via Wnt/β-catenin signaling. Exp Ther Med. 2019; 17(6):4703-4708. PMC: 6489056. DOI: 10.3892/etm.2019.7468. View

Sheng N, Xu Y, Xi Q, Jiang H, Wang C, Zhang Y . Overexpression of KIF2A is Suppressed by miR-206 and Associated with Poor Prognosis in Ovarian Cancer. Cell Physiol Biochem. 2018; 50(3):810-822. DOI: 10.1159/000494467. View

Zhang X, Ma C, Wang Q, Liu J, Tian M, Yuan Y . Role of KIF2A in the progression and metastasis of human glioma. Mol Med Rep. 2015; 13(2):1781-7. DOI: 10.3892/mmr.2015.4700. View

10.

Zhao P, Lan F, Zhang H, Zeng G, Liu D . Down-regulation of KIF2A inhibits gastric cancer cell invasion via suppressing MT1-MMP. Clin Exp Pharmacol Physiol. 2018; 45(10):1010-1018. DOI: 10.1111/1440-1681.12974. View

11.

Li X, Liang J, Liu Y, Wang Y, Yang X, Luan B . miR-149 reverses cisplatin resistance of gastric cancer SGC7901/DDP cells by targeting FoxM1. Pharmazie. 2018; 71(11):640-643. DOI: 10.1691/ph.2016.6696. View

12.

Song H, Zhu J, Lu D . Molecular-targeted first-line therapy for advanced gastric cancer. Cochrane Database Syst Rev. 2016; 7:CD011461. PMC: 6457914. DOI: 10.1002/14651858.CD011461.pub2. View

13.

Wang Y, Zheng X, Zhang Z, Zhou J, Zhao G, Yang J . MicroRNA-149 inhibits proliferation and cell cycle progression through the targeting of ZBTB2 in human gastric cancer. PLoS One. 2012; 7(10):e41693. PMC: 3483266. DOI: 10.1371/journal.pone.0041693. View

14.

Wang J, Ma S, Ma R, Qu X, Liu W, Lv C . KIF2A silencing inhibits the proliferation and migration of breast cancer cells and correlates with unfavorable prognosis in breast cancer. BMC Cancer. 2014; 14:461. PMC: 4076253. DOI: 10.1186/1471-2407-14-461. View

15.

Feng R, Chen X, Yu Y, Su L, Yu B, Li J . miR-126 functions as a tumour suppressor in human gastric cancer. Cancer Lett. 2010; 298(1):50-63. DOI: 10.1016/j.canlet.2010.06.004. View

16.

Shan D, Shang Y, Hu T . Long noncoding RNA BLACAT1 promotes cell proliferation and invasion in human cervical cancer. Oncol Lett. 2018; 15(3):3490-3495. PMC: 5795854. DOI: 10.3892/ol.2018.7773. View

17.

Xu M, Wang Y, Weng W, Wei P, Qi P, Zhang Q . A Positive Feedback Loop of lncRNA- and FOXM1 Facilitates Gastric Cancer Growth and Invasion. Clin Cancer Res. 2016; 23(8):2071-2080. DOI: 10.1158/1078-0432.CCR-16-0742. View

18.

Yao X, Tang J, Zhu H, Jing Y . High expression of LncRNA CASC15 is a risk factor for gastric cancer prognosis and promote the proliferation of gastric cancer. Eur Rev Med Pharmacol Sci. 2017; 21(24):5661-5667. DOI: 10.26355/eurrev_201712_14010. View

19.

Shao Y, Ye M, Li Q, Sun W, Ye G, Zhang X . LncRNA-RMRP promotes carcinogenesis by acting as a miR-206 sponge and is used as a novel biomarker for gastric cancer. Oncotarget. 2016; 7(25):37812-37824. PMC: 5122351. DOI: 10.18632/oncotarget.9336. View

20.

Su J, Zhang E, Han L, Yin D, Liu Z, He X . Long noncoding RNA BLACAT1 indicates a poor prognosis of colorectal cancer and affects cell proliferation by epigenetically silencing of p15. Cell Death Dis. 2017; 8(3):e2665. PMC: 5386575. DOI: 10.1038/cddis.2017.83. View