LncRNA LINC00673 Induces Proliferation, Metastasis and Epithelial-mesenchymal Transition in Thyroid Carcinoma Via Kruppel-like Factor 2

Overview

Journal Int J Oncol

Specialty Oncology

Date 2018 Aug 15

PMID 30106140

Citations 23

Authors

Erjie Xia

Adheesh Bhandari

Yanyan Shen

Xiaofen Zhou

Ouchen Wang

Affiliations

Soon will be listed here.

Abstract

The incidence of thyroid cancer has increased in the past decades; however, the underlying molecular mechanisms of thyroid cancer tumorigenesis remain unknown. Using sequencing technology, long intergenic non‑protein coding RNA 673 (LINC00673) was identified to be upregulated in several tumor tissues. However, the biological role of LINC00673 in thyroid carcinoma has yet to be determined. In this study, 60 matched pairs of thyroid tumor tissue and normal tissue were selected for study using reverse transcription-quantitative polymerase chain reaction (RT-qPCR) to validate previous findings; then, clinicopathologic features of the tissues were analyzed. Proliferation, colony formation, migration and invasion assays were performed, and epithelial-mesenchymal transition (EMT)-associated phenotypes were investigated following transfection with small interfering RNA to determine the specific role of LINC00673 in thyroid carcinoma cell lines (TPC1, KTC‑1 and BCPAP). The study revealed that long non‑coding RNA LINC00673 was significantly upregulated in thyroid cancer tissues compared with paired adjacent non‑tumor tissues using RT-qPCR and that high expression of LINC00673 is was associated with larger tumor size and lymph node metastasis in the validated cohort. Knockdown of LINC00673 inhibited cell proliferation and metastasis, whereas, LINC00673 overexpression had the opposite effect. The results showed that LINC00673 may influence EMT and the expression of Kruppel-like factor 2 (KLF2). Notably, KLF2 is considered a tumor suppressor gene in a variety of tumors. Finally, knock down of KLF2 enhanced thyroid carcinoma cell proliferation, and invasion and migration. In this study, the function of LINC00673 in promoting the proliferation and metastasis of thyroid carcinoma cell lines was identified, and LINC00673 may act as a novel therapeutic target for treating thyroid carcinoma.

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References

Abdul-Rahman U, Gyorffy B, Adams B . linc00673 (ERRLR01) is a prognostic indicator of overall survival in breast cancer. Transcription. 2017; 9(1):17-29. PMC: 5791815. DOI: 10.1080/21541264.2017.1329684. View

Lu W, Zhang H, Niu Y, Wu Y, Sun W, Li H . Long non-coding RNA linc00673 regulated non-small cell lung cancer proliferation, migration, invasion and epithelial mesenchymal transition by sponging miR-150-5p. Mol Cancer. 2017; 16(1):118. PMC: 5504775. DOI: 10.1186/s12943-017-0685-9. View

Yue B, Cai D, Liu C, Fang C, Yan D . Linc00152 Functions as a Competing Endogenous RNA to Confer Oxaliplatin Resistance and Holds Prognostic Values in Colon Cancer. Mol Ther. 2016; 24(12):2064-2077. PMC: 5167786. DOI: 10.1038/mt.2016.180. View

Wen X, Han X, Wang Y, Fan S, Zhuang J, Zhang Z . Effects of long noncoding RNA SPRY4-IT1-mediated EZH2 on the invasion and migration of lung adenocarcinoma. J Cell Biochem. 2017; 119(2):1827-1840. DOI: 10.1002/jcb.26344. View

Xia E, Bhandari A, Shen Y, Zhou X, Sindan N, Xiang J . LncRNA CCND2-AS1 promotes proliferation, migration, and invasion in papillary thyroid carcinoma. Biochem Biophys Res Commun. 2018; 496(2):628-632. DOI: 10.1016/j.bbrc.2018.01.102. View

Li Q, Zhang C, Chen R, Xiong H, Qiu F, Liu S . Disrupting MALAT1/miR-200c sponge decreases invasion and migration in endometrioid endometrial carcinoma. Cancer Lett. 2016; 383(1):28-40. DOI: 10.1016/j.canlet.2016.09.019. View

Siegel R, Miller K, Jemal A . Cancer statistics, 2018. CA Cancer J Clin. 2018; 68(1):7-30. DOI: 10.3322/caac.21442. View

Xu T, Liu X, Xia R, Yin L, Kong R, Chen W . SP1-induced upregulation of the long noncoding RNA TINCR regulates cell proliferation and apoptosis by affecting KLF2 mRNA stability in gastric cancer. Oncogene. 2015; 34(45):5648-61. DOI: 10.1038/onc.2015.18. View

Lan X, Sun W, Dong W, Wang Z, Zhang T, He L . Downregulation of long noncoding RNA H19 contributes to the proliferation and migration of papillary thyroid carcinoma. Gene. 2017; 646:98-105. DOI: 10.1016/j.gene.2017.12.051. View

10.

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

11.

Thiery J, Acloque H, Huang R, Nieto M . Epithelial-mesenchymal transitions in development and disease. Cell. 2009; 139(5):871-90. DOI: 10.1016/j.cell.2009.11.007. View

12.

Qian K, Liu G, Tang Z, Hu Y, Fang Y, Chen Z . The long non-coding RNA NEAT1 interacted with miR-101 modulates breast cancer growth by targeting EZH2. Arch Biochem Biophys. 2016; 615:1-9. DOI: 10.1016/j.abb.2016.12.011. View

13.

Rahib L, Smith B, Aizenberg R, Rosenzweig A, Fleshman J, Matrisian L . Projecting cancer incidence and deaths to 2030: the unexpected burden of thyroid, liver, and pancreas cancers in the United States. Cancer Res. 2014; 74(11):2913-21. DOI: 10.1158/0008-5472.CAN-14-0155. View

14.

Chu Y, Hardin H, Schneider D, Chen H, Lloyd R . MicroRNA-21 and long non-coding RNA MALAT1 are overexpressed markers in medullary thyroid carcinoma. Exp Mol Pathol. 2017; 103(2):229-236. DOI: 10.1016/j.yexmp.2017.10.002. View

15.

Yu J, Liu Y, Gong Z, Zhang S, Guo C, Li X . Overexpression long non-coding RNA LINC00673 is associated with poor prognosis and promotes invasion and metastasis in tongue squamous cell carcinoma. Oncotarget. 2017; 8(10):16621-16632. PMC: 5369989. DOI: 10.18632/oncotarget.14200. View

16.

Ma C, Wu G, Zhu Q, Liu H, Yao Y, Yuan D . Long intergenic noncoding RNA 00673 promotes non-small-cell lung cancer metastasis by binding with EZH2 and causing epigenetic silencing of HOXA5. Oncotarget. 2017; 8(20):32696-32705. PMC: 5464820. DOI: 10.18632/oncotarget.16158. View

17.

Prescott J, Zeiger M . The RET oncogene in papillary thyroid carcinoma. Cancer. 2015; 121(13):2137-46. DOI: 10.1002/cncr.29044. View

18.

Huang M, Hou J, Wang Y, Xie M, Wei C, Nie F . Long Noncoding RNA LINC00673 Is Activated by SP1 and Exerts Oncogenic Properties by Interacting with LSD1 and EZH2 in Gastric Cancer. Mol Ther. 2017; 25(4):1014-1026. PMC: 5383578. DOI: 10.1016/j.ymthe.2017.01.017. View

19.

Gou X, Zhao X, Wang Z . Long noncoding RNA PVT1 promotes hepatocellular carcinoma progression through regulating miR-214. Cancer Biomark. 2017; 20(4):511-519. DOI: 10.3233/CBM-170331. View

20.

Gong Z, Zhang S, Zhang W, Huang H, Li Q, Deng H . Long non-coding RNAs in cancer. Sci China Life Sci. 2012; 55(12):1120-4. DOI: 10.1007/s11427-012-4413-9. View