Skip to main content
Top
Published in: Cancer Cell International 1/2019

Open Access 01-12-2019 | Metastasis | Primary research

Long non-coding RNA CASC2 upregulates PTEN to suppress pancreatic carcinoma cell metastasis by downregulating miR-21

Authors: Hui Zhang, Xielin Feng, Mingyi Zhang, Aixiang Liu, Lang Tian, Wentao Bo, Haiqing Wang, Yong Hu

Published in: Cancer Cell International | Issue 1/2019

Login to get access

Abstract

Background

The mechanism of pancreatic cancer metastasis remains poorly understood. Recently, lncRNA CASC2 has been demonstrated to be a tumor suppressor in various types of cancer. This study aimed to explore the mechanism of CASC2 in the regulation of pancreatic cancer metastasis.

Methods

The expression levels of CASC2 and miR-21 in pancreatic cells were detected by qRT-PCR. Using specific expression vectors, including mimics or shRNA, the expression levels of CASC2, miR-21 and PTEN in pancreatic cells were altered. The association between CASC2, miR-21 and PTEN was detected. Then, cell migration and invasion were assessed using the transwell assay.

Results

CASC2 expression was downregulated in the pancreatic cancer cell lines CAPAN-1, BxPC-3, JF305, PANC-1 and SW1990 compared with levels in normal human pancreatic HPDE6-C7 cells. CACS2 overexpression inhibited the migration and invasion of PANC-1 cells and significantly inhibited the expression of miR-21 and PTEN. MiR-21 was a direct target of CACS2. The overexpression of miR-21 significantly abolished the antimetastatic effects of CASC2 on PANC-1 cells. Moreover, the downregulation of PTEN significantly abolished the antimetastatic effects of CASC2.

Conclusion

CASC2 functions as a tumor suppressor in pancreatic cancer cells to inhibit tumor cell migration and invasion. Our work revealed a novel regulatory mechanism of the CASC2/miR-21/PTEN axis that may be important in pancreatic cancer.
Literature
1.
go back to reference Lin QJ, Yang F, Jin C, Fu DL. Current status and progress of pancreatic cancer in China. World J Gastroenterol. 2015;21(26):7988–8003.CrossRef Lin QJ, Yang F, Jin C, Fu DL. Current status and progress of pancreatic cancer in China. World J Gastroenterol. 2015;21(26):7988–8003.CrossRef
2.
go back to reference Shuaichen L, Guangyi W. Relating pancreatic ductal adenocarcinoma tumor samples and cell lines using gene expression data in translational research. Cell Mol (Biol Noisy-le-grand). 2018;64(5):157–62.CrossRef Shuaichen L, Guangyi W. Relating pancreatic ductal adenocarcinoma tumor samples and cell lines using gene expression data in translational research. Cell Mol (Biol Noisy-le-grand). 2018;64(5):157–62.CrossRef
3.
go back to reference Zeng Y. Advances in mechanism and treatment strategy of cancer. Cell Mol Biol (Noisy-le-grand). 2018;64(6):1–3.CrossRef Zeng Y. Advances in mechanism and treatment strategy of cancer. Cell Mol Biol (Noisy-le-grand). 2018;64(6):1–3.CrossRef
4.
go back to reference Thomson DW, Dinger ME. Endogenous microRNA sponges: evidence and controversy. Nat Rev Genet. 2016;17(5):272–83.CrossRef Thomson DW, Dinger ME. Endogenous microRNA sponges: evidence and controversy. Nat Rev Genet. 2016;17(5):272–83.CrossRef
5.
go back to reference Chan JJ, Tay Y. Noncoding RNA:RNA regulatory networks in cancer. Int J Mol Sci. 2018;19:5. Chan JJ, Tay Y. Noncoding RNA:RNA regulatory networks in cancer. Int J Mol Sci. 2018;19:5.
6.
go back to reference Renganathan A, Felley-Bosco E. Long noncoding RNAs in cancer and therapeutic potential. Adv Exp Med Biol. 2017;1008:199–222.CrossRef Renganathan A, Felley-Bosco E. Long noncoding RNAs in cancer and therapeutic potential. Adv Exp Med Biol. 2017;1008:199–222.CrossRef
7.
go back to reference Palmieri G, Paliogiannis P, Sini MC, Manca A, Palomba G, Doneddu V, Tanda F, Pascale MR, Cossu A. Long non-coding RNA CASC2 in human cancer. Crit Rev Oncol Hematol. 2017;111:31–8.CrossRef Palmieri G, Paliogiannis P, Sini MC, Manca A, Palomba G, Doneddu V, Tanda F, Pascale MR, Cossu A. Long non-coding RNA CASC2 in human cancer. Crit Rev Oncol Hematol. 2017;111:31–8.CrossRef
8.
go back to reference Yu X, Zheng H, Tse G, Zhang L, Wu WKK. CASC2: An emerging tumour-suppressing long noncoding RNA in human cancers and melanoma. Cell Prolif. 2018;51:e12506.CrossRef Yu X, Zheng H, Tse G, Zhang L, Wu WKK. CASC2: An emerging tumour-suppressing long noncoding RNA in human cancers and melanoma. Cell Prolif. 2018;51:e12506.CrossRef
10.
go back to reference Simonian M, Sharifi M, Nedaeinia R, Mosallaie M, Khosravi S, Avan A, Ghayour-Mobarhan M, Bagheri H, Salehi R. Evaluation of miR-21 inhibition and its impact on cancer susceptibility candidate 2 long noncoding RNA in colorectal cancer cell line. Adv Biomed Res. 2018;7:14.CrossRef Simonian M, Sharifi M, Nedaeinia R, Mosallaie M, Khosravi S, Avan A, Ghayour-Mobarhan M, Bagheri H, Salehi R. Evaluation of miR-21 inhibition and its impact on cancer susceptibility candidate 2 long noncoding RNA in colorectal cancer cell line. Adv Biomed Res. 2018;7:14.CrossRef
11.
go back to reference Feng Y, Zou W, Hu C, Li G, Zhou S, He Y, Ma F, Deng C, Sun L. Modulation of CASC2/miR-21/PTEN pathway sensitizes cervical cancer to cisplatin. Arch Biochem Biophys. 2017;623–624:20–30.CrossRef Feng Y, Zou W, Hu C, Li G, Zhou S, He Y, Ma F, Deng C, Sun L. Modulation of CASC2/miR-21/PTEN pathway sensitizes cervical cancer to cisplatin. Arch Biochem Biophys. 2017;623–624:20–30.CrossRef
12.
go back to reference Yang L, Zhang Y, Ling C, Heng W. RNPC1 inhibits non-small cell lung cancer progression via regulating miR-181a/CASC2 axis. Biotechnol Lett. 2018;40(3):543–50.CrossRef Yang L, Zhang Y, Ling C, Heng W. RNPC1 inhibits non-small cell lung cancer progression via regulating miR-181a/CASC2 axis. Biotechnol Lett. 2018;40(3):543–50.CrossRef
13.
go back to reference Liao Y, Shen L, Zhao H, Liu Q, Fu J, Guo Y, Peng R, Cheng L. LncRNA CASC2 interacts with miR-181a to modulate glioma growth and resistance to TMZ through PTEN pathway. J Cell Biochem. 2017;118(7):1889–99.CrossRef Liao Y, Shen L, Zhao H, Liu Q, Fu J, Guo Y, Peng R, Cheng L. LncRNA CASC2 interacts with miR-181a to modulate glioma growth and resistance to TMZ through PTEN pathway. J Cell Biochem. 2017;118(7):1889–99.CrossRef
15.
go back to reference Jiang C, Shen F, Du J, Fang X, Li X, Su J, Wang X, Huang X, Liu Z. Upregulation of CASC2 sensitized glioma to temozolomide cytotoxicity through autophagy inhibition by sponging miR-193a-5p and regulating mTOR expression. Biomed Pharmacother. 2018;97:844–50.CrossRef Jiang C, Shen F, Du J, Fang X, Li X, Su J, Wang X, Huang X, Liu Z. Upregulation of CASC2 sensitized glioma to temozolomide cytotoxicity through autophagy inhibition by sponging miR-193a-5p and regulating mTOR expression. Biomed Pharmacother. 2018;97:844–50.CrossRef
16.
go back to reference Wang Y, Liu Z, Yao B, Li Q, Wang L, Wang C, Dou C, Xu M, Liu Q, Tu K. Long non-coding RNA CASC2 suppresses epithelial–mesenchymal transition of hepatocellular carcinoma cells through CASC2/miR-367/FBXW7 axis. Mol Cancer. 2017;16(1):123.CrossRef Wang Y, Liu Z, Yao B, Li Q, Wang L, Wang C, Dou C, Xu M, Liu Q, Tu K. Long non-coding RNA CASC2 suppresses epithelial–mesenchymal transition of hepatocellular carcinoma cells through CASC2/miR-367/FBXW7 axis. Mol Cancer. 2017;16(1):123.CrossRef
17.
go back to reference Chan JA, Krichevsky AM, Kosik KS. MicroRNA-21 is an antiapoptotic factor in human glioblastoma cells. Can Res. 2005;65(14):6029–33.CrossRef Chan JA, Krichevsky AM, Kosik KS. MicroRNA-21 is an antiapoptotic factor in human glioblastoma cells. Can Res. 2005;65(14):6029–33.CrossRef
18.
go back to reference Meng F, Henson R, Wehbe-Janek H, Ghoshal K, Jacob ST, Patel T. MicroRNA-21 regulates expression of the PTEN tumor suppressor gene in human hepatocellular cancer. Gastroenterology. 2007;133(2):647–58.CrossRef Meng F, Henson R, Wehbe-Janek H, Ghoshal K, Jacob ST, Patel T. MicroRNA-21 regulates expression of the PTEN tumor suppressor gene in human hepatocellular cancer. Gastroenterology. 2007;133(2):647–58.CrossRef
19.
go back to reference Pfeffer SR, Yang CH, Pfeffer LM. The role of miR-21 in cancer. Drug Dev Res. 2015;76(6):270–7.CrossRef Pfeffer SR, Yang CH, Pfeffer LM. The role of miR-21 in cancer. Drug Dev Res. 2015;76(6):270–7.CrossRef
20.
go back to reference Wang H, Hang C, Ou XL, Nie JS, Ding YT, Xue SG, Gao H, Zhu JX. MiR-145 functions as a tumor suppressor via regulating angiopoietin-2 in pancreatic cancer cells. Cancer Cell Int. 2016;16(1):65.CrossRef Wang H, Hang C, Ou XL, Nie JS, Ding YT, Xue SG, Gao H, Zhu JX. MiR-145 functions as a tumor suppressor via regulating angiopoietin-2 in pancreatic cancer cells. Cancer Cell Int. 2016;16(1):65.CrossRef
21.
go back to reference Zhu W, Xu B. MicroRNA-21 identified as predictor of cancer outcome: a meta-analysis. PLoS ONE. 2014;9(8):e103373.CrossRef Zhu W, Xu B. MicroRNA-21 identified as predictor of cancer outcome: a meta-analysis. PLoS ONE. 2014;9(8):e103373.CrossRef
22.
go back to reference Zeng Y, Yao X, Chen L, Yan Z, Liu J, Zhang Y, Feng T, Wu J, Liu X. Sphingosine-1-phosphate induced epithelial–mesenchymal transition of hepatocellular carcinoma via an MMP-7/syndecan-1/TGF-beta autocrine loop. Oncotarget. 2016;7(39):63324–37.CrossRef Zeng Y, Yao X, Chen L, Yan Z, Liu J, Zhang Y, Feng T, Wu J, Liu X. Sphingosine-1-phosphate induced epithelial–mesenchymal transition of hepatocellular carcinoma via an MMP-7/syndecan-1/TGF-beta autocrine loop. Oncotarget. 2016;7(39):63324–37.CrossRef
23.
go back to reference Deer EL, Gonzalez-Hernandez J, Coursen JD, Shea JE, Ngatia J, Scaife CL, Firpo MA, Mulvihill SJ. Phenotype and genotype of pancreatic cancer cell lines. Pancreas. 2010;39(4):425–35.CrossRef Deer EL, Gonzalez-Hernandez J, Coursen JD, Shea JE, Ngatia J, Scaife CL, Firpo MA, Mulvihill SJ. Phenotype and genotype of pancreatic cancer cell lines. Pancreas. 2010;39(4):425–35.CrossRef
24.
go back to reference Zhao MY, Wang LM, Liu J, Huang X, Liu J, Zhang YF. MiR-21 suppresses anoikis through targeting PDCD4 and PTEN in human esophageal adenocarcinoma. Curr Med Sci. 2018;38(2):245–51.CrossRef Zhao MY, Wang LM, Liu J, Huang X, Liu J, Zhang YF. MiR-21 suppresses anoikis through targeting PDCD4 and PTEN in human esophageal adenocarcinoma. Curr Med Sci. 2018;38(2):245–51.CrossRef
25.
go back to reference Zhao L, Zhang X, Cui S. Matrine inhibits TPC-1 human thyroid cancer cells via the miR-21/PTEN/Akt pathway. Oncol Lett. 2018;16(3):2965–70.PubMedPubMedCentral Zhao L, Zhang X, Cui S. Matrine inhibits TPC-1 human thyroid cancer cells via the miR-21/PTEN/Akt pathway. Oncol Lett. 2018;16(3):2965–70.PubMedPubMedCentral
26.
go back to reference Liu H, Cheng L, Cao D, Zhang H. Suppression of miR-21 expression inhibits cell proliferation and migration of liver cancer cells by targeting phosphatase and tensin homolog (PTEN). Med Sci Monit. 2018;24:3571–7.CrossRef Liu H, Cheng L, Cao D, Zhang H. Suppression of miR-21 expression inhibits cell proliferation and migration of liver cancer cells by targeting phosphatase and tensin homolog (PTEN). Med Sci Monit. 2018;24:3571–7.CrossRef
27.
go back to reference Wang X, Luo G, Zhang K, Cao J, Huang C, Jiang T, Liu B, Su L, Qiu Z. Hypoxic tumor-derived exosomal miR-301a mediates M2 macrophage polarization via PTEN/PI3Kgamma to promote pancreatic cancer metastasis. Can Res. 2018;78(16):4586–98.CrossRef Wang X, Luo G, Zhang K, Cao J, Huang C, Jiang T, Liu B, Su L, Qiu Z. Hypoxic tumor-derived exosomal miR-301a mediates M2 macrophage polarization via PTEN/PI3Kgamma to promote pancreatic cancer metastasis. Can Res. 2018;78(16):4586–98.CrossRef
28.
go back to reference Gao ZQ, Wang JF, Chen DH, Ma XS, Wu Y, Tang Z, Dang XW. Long non-coding RNA GAS5 suppresses pancreatic cancer metastasis through modulating miR-32-5p/PTEN axis. Cell Biosci. 2017;7:66.CrossRef Gao ZQ, Wang JF, Chen DH, Ma XS, Wu Y, Tang Z, Dang XW. Long non-coding RNA GAS5 suppresses pancreatic cancer metastasis through modulating miR-32-5p/PTEN axis. Cell Biosci. 2017;7:66.CrossRef
29.
go back to reference Yan X, Zhu Y, Li F, Shi W, Wang J, Wang Q, Zhang Q, Chai L, Li M. The value of long noncoding RNA CASC2 as a biomarker of prognosis in carcinomas: a meta-analysis. J Cancer. 2018;9(21):3824–30.CrossRef Yan X, Zhu Y, Li F, Shi W, Wang J, Wang Q, Zhang Q, Chai L, Li M. The value of long noncoding RNA CASC2 as a biomarker of prognosis in carcinomas: a meta-analysis. J Cancer. 2018;9(21):3824–30.CrossRef
30.
go back to reference Yu L, Chen S, Bao H, Zhang W, Liao M, Liang Q, Cheng X. The role of lncRNA CASC2 on prognosis of malignant tumors: a meta-analysis and bioinformatics. OncoTargets Ther. 2018;11:4355–65.CrossRef Yu L, Chen S, Bao H, Zhang W, Liao M, Liang Q, Cheng X. The role of lncRNA CASC2 on prognosis of malignant tumors: a meta-analysis and bioinformatics. OncoTargets Ther. 2018;11:4355–65.CrossRef
Metadata
Title
Long non-coding RNA CASC2 upregulates PTEN to suppress pancreatic carcinoma cell metastasis by downregulating miR-21
Authors
Hui Zhang
Xielin Feng
Mingyi Zhang
Aixiang Liu
Lang Tian
Wentao Bo
Haiqing Wang
Yong Hu
Publication date
01-12-2019
Publisher
BioMed Central
Published in
Cancer Cell International / Issue 1/2019
Electronic ISSN: 1475-2867
DOI
https://doi.org/10.1186/s12935-019-0728-y

Other articles of this Issue 1/2019

Cancer Cell International 1/2019 Go to the issue
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine