Long non-coding RNA CUDR promotes malignant phenotypes in pancreatic ductal adenocarcinoma via activating AKT and ERK signaling pathways

  • Authors:
    • Xing Liang
    • Meiyan Qi
    • Rui Wu
    • Anan Liu
    • Danlei Chen
    • Liang Tang
    • Jun Chen
    • Xiangui Hu
    • Wei Li
    • Lixing Zhan
    • Chenghao Shao
  • View Affiliations

  • Published online on: September 27, 2018     https://doi.org/10.3892/ijo.2018.4574
  • Pages: 2671-2682
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )


Abstract

Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal malignancies, with a marked potential for invasion and metastasis. Emerging evidence has suggested that dysregulation of long non-coding RNAs (lncRNAs) is associated with the development of multiple types of cancer. However, the function of lncRNAs in PDAC is poorly known. In the present study, a microarray assay was used to screen for differently expressed lncRNAs in PDAC and it was identified that cancer upregulated drug resistance (CUDR) was upregulated in PDAC. CUDR increased PDAC cell proliferation, migration and invasion, inhibited apoptosis, and promoted drug resistance; it also regulated the PDAC cell epithelial-mesenchymal transition. The CUDR-induced PDAC malignant phenotypes is via the protein kinase B and extracellular-signal-regulated kinase signaling pathways. Downregulation of CUDR may be a novel therapeutic strategy to prevent PDAC development and drug resistance in the future.

References

1 

Siegel RL, Miller KD and Jemal A: Cancer statistics, 2018. CA Cancer J Clin. 68:7–30. 2018. View Article : Google Scholar : PubMed/NCBI

2 

Poruk KE, Firpo MA, Adler DG and Mulvihill SJ: Screening for pancreatic cancer: Why, how, and who? Ann Surg. 257:17–26. 2013. View Article : Google Scholar

3 

Ryan DP, Hong TS and Bardeesy N: Pancreatic adenocarcinoma. N Engl J Med. 371:1039–1049. 2014. View Article : Google Scholar : PubMed/NCBI

4 

Uesaka K, Boku N, Fukutomi A, Okamura Y, Konishi M, Matsumoto I, Kaneoka Y, Shimizu Y, Nakamori S, Sakamoto H, et al JASPAC 01 Study Group: Adjuvant chemotherapy of S-1 versus gemcitabine for resected pancreatic cancer: A phase 3, open-label, randomised, non-inferiority trial (JASPAC 01). Lancet. 388:248–257. 2016. View Article : Google Scholar : PubMed/NCBI

5 

Xiong XD, Ren X, Cai MY, Yang JW, Liu X and Yang JM: Long non-coding RNAs: An emerging powerhouse in the battle between life and death of tumor cells. Drug Resist Updat. 26:28–42. 2016. View Article : Google Scholar : PubMed/NCBI

6 

Qi P and Du X: The long non-coding RNAs, a new cancer diagnostic and therapeutic gold mine. Mod Pathol. 26:155–165. 2013. View Article : Google Scholar

7 

Xie Z, Chen X, Li J, Guo Y, Li H, Pan X, Jiang J, Liu H and Wu B: Salivary HOTAIR and PVT1 as novel biomarkers for early pancreatic cancer. Oncotarget. 7:25408–25419. 2016.PubMed/NCBI

8 

Zheng S, Chen H, Wang Y, Gao W, Fu Z, Zhou Q, Jiang Y, Lin Q, Tan L, Ye H, et al: Long non-coding RNA LOC389641 promotes progression of pancreatic ductal adenocarcinoma and increases cell invasion by regulating E-cadherin in a TNFRSF10A-related manner. Cancer Lett. 371:354–365. 2016. View Article : Google Scholar

9 

Li X, Deng SJ, Zhu S, Jin Y, Cui SP, Chen JY, Xiang C, Li QY, He C, Zhao SF, et al: Hypoxia-induced lncRNA-NUTF2P3-001 contributes to tumorigenesis of pancreatic cancer by derepressing the miR-3923/KRAS pathway. Oncotarget. 7:6000–6014. 2016.PubMed/NCBI

10 

Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods. 25:402–408. 2001. View Article : Google Scholar

11 

Zhang X, Sun S, Pu JK, Tsang AC, Lee D, Man VO, Lui WM, Wong ST and Leung GK: Long non-coding RNA expression profiles predict clinical phenotypes in glioma. Neurobiol Dis. 48:1–8. 2012. View Article : Google Scholar : PubMed/NCBI

12 

Harrow J, Denoeud F, Frankish A, Reymond A, Chen CK, Chrast J, Lagarde J, Gilbert JG, Storey R, Swarbreck D, et al: GENCODE: producing a reference annotation for ENCODE. Genome Biol. 7(Suppl 1): S41–9. 2006. View Article : Google Scholar : PubMed/NCBI

13 

Ørom UA, Derrien T, Beringer M, Gumireddy K, Gardini A, Bussotti G, Lai F, Zytnicki M, Notredame C, Huang Q, et al: Long noncoding RNAs with enhancer-like function in human cells. Cell. 143:46–58. 2010. View Article : Google Scholar : PubMed/NCBI

14 

Guttman M, Amit I, Garber M, French C, Lin MF, Feldser D, Huarte M, Zuk O, Carey BW, Cassady JP, et al: Chromatin signature reveals over a thousand highly conserved large non-coding RNAs in mammals. Nature. 458:223–227. 2009. View Article : Google Scholar : PubMed/NCBI

15 

Miyake T, Honma Y, Urano T, Kato N and Suzumiya J: Combined treatment with tamoxifen and a fusicoccin derivative (ISIR-042) to overcome resistance to therapy and to enhance the antitumor activity of 5-fluorouracil and gemcitabine in pancreatic cancer cells. Int J Oncol. 47:315–324. 2015. View Article : Google Scholar : PubMed/NCBI

16 

Wang Y, Chen W, Yang C, Wu W, Wu S, Qin X and Li X: Long non-coding RNA UCA1a(CUDR) promotes proliferation and tumorigenesis of bladder cancer. Int J Oncol. 41:276–284. 2012.PubMed/NCBI

17 

Tsang WP, Wong TWL, Cheung AHH, Co CNN and Kwok TT: Induction of drug resistance and transformation in human cancer cells by the noncoding RNA CUDR. RNA. 13:890–898. 2007. View Article : Google Scholar : PubMed/NCBI

18 

Huang J, Zhou N, Watabe K, Lu Z, Wu F, Xu M and Mo YY: Long non-coding RNA UCA1 promotes breast tumor growth by suppression of p27 (Kip1). Cell Death Dis. 5:e10082014. View Article : Google Scholar : PubMed/NCBI

19 

Pu H, Zheng Q, Li H, Wu M, An J, Gui X, Li T and Lu D: CUDR promotes liver cancer stem cell growth through upregulating TERT and C-Myc. Oncotarget. 6:40775–40798. 2015. View Article : Google Scholar : PubMed/NCBI

20 

Han Y, Yang YN, Yuan HH, Zhang TT, Sui H, Wei XL, Liu L, Huang P, Zhang WJ and Bai YX: UCA1, a long non-coding RNA up-regulated in colorectal cancer influences cell proliferation, apoptosis and cell cycle distribution. Pathology. 46:396–401. 2014. View Article : Google Scholar : PubMed/NCBI

21 

Zheng Q, Wu F, Dai WY, Zheng DC, Zheng C, Ye H, Zhou B, Chen JJ and Chen P: Aberrant expression of UCA1 in gastric cancer and its clinical significance. Clin Transl Oncol. 17:640–646. 2015. View Article : Google Scholar : PubMed/NCBI

22 

Fang Z, Wu L, Wang L, Yang Y, Meng Y and Yang H: Increased expression of the long non-coding RNA UCA1 in tongue squamous cell carcinomas: A possible correlation with cancer metastasis. Oral Surg Oral Med Oral Pathol Oral Radiol. 117:89–95. 2014. View Article : Google Scholar

23 

Chen P, Wan D, Zheng D, Zheng Q, Wu F and Zhi Q: Long non-coding RNA UCA1 promotes the tumorigenesis in pancreatic cancer. Biomed Pharmacother. 83:1220–1226. 2016. View Article : Google Scholar : PubMed/NCBI

24 

Fu XL, Liu DJ, Yan TT, Yang JY, Yang MW, Li J, Huo YM, Liu W, Zhang JF, Hong J, et al: Analysis of long non-coding RNA expression profiles in pancreatic ductal adenocarcinoma. Sci Rep. 6:335352016. View Article : Google Scholar : PubMed/NCBI

25 

Zhang X, Gao F, Zhou L, Wang H, Shi G and Tan X: UCA1 regulates the growth and metastasis of pancreatic cancer by sponging miR-135a. Oncol Res. 25:1529–1541. 2017. View Article : Google Scholar : PubMed/NCBI

26 

Cheng N, Cai W, Ren S, Li X, Wang Q, Pan H, Zhao M, Li J, Zhang Y, Zhao C, et al: Long non-coding RNA UCA1 induces non-T790M acquired resistance to EGFR-TKIs by activating the AKT/mTOR pathway in EGFR-mutant non-small cell lung cancer. Oncotarget. 6:23582–23593. 2015. View Article : Google Scholar : PubMed/NCBI

27 

Wang ZQ, Cai Q, Hu L, He CY, Li JF, Quan ZW, Liu BY, Li C and Zhu ZG: Long noncoding RNA UCA1 induced by SP1 promotes cell proliferation via recruiting EZH2 and activating AKT pathway in gastric cancer. Cell Death Dis. 8:e28392017. View Article : Google Scholar : PubMed/NCBI

28 

Pan JJ and Yang MH: The role of epithelial-mesenchymal transition in pancreatic cancer. J Gastrointest Oncol. 2:151–156. 2011.

29 

Zhan HX, Wang Y, Li C, Xu JW, Zhou B, Zhu JK, Han HF, Wang L, Wang YS and Hu SY: LincRNA-ROR promotes invasion, metastasis and tumor growth in pancreatic cancer through activating ZEB1 pathway. Cancer Lett. 374:261–271. 2016. View Article : Google Scholar : PubMed/NCBI

30 

Jiao F, Hu H, Yuan C and Wang L, Jiang W, Jin Z, Guo Z and Wang L: Elevated expression level of long noncoding RNA MALAT-1 facilitates cell growth, migration and invasion in pancreatic cancer. Oncol Rep. 32:2485–2492. 2014. View Article : Google Scholar : PubMed/NCBI

31 

Ma L, Wang F, Du C, Zhang Z, Guo H, Xie X, Gao H, Zhuang Y, Kornmann M, Gao H, et al: Long non-coding RNA MEG3 functions as a tumour suppressor and has prognostic predictive value in human pancreatic cancer. Oncol Rep. 39:1132–1140. 2018.PubMed/NCBI

32 

Ren Y, Jia HH, Xu YQ, Zhou X, Zhao XH, Wang YF, Song X, Zhu ZY, Sun T, Dou Y, et al: Paracrine and epigenetic control of CAF-induced metastasis: The role of HOTAIR stimulated by TGF-ß1 secretion. Mol Cancer. 17:52018. View Article : Google Scholar

33 

Ma C, Nong K, Zhu H, Wang W, Huang X, Yuan Z and Ai K: H19 promotes pancreatic cancer metastasis by derepressing let-7’s suppression on its target HMGA2-mediated EMT. Tumour Biol. 35:9163–9169. 2014. View Article : Google Scholar : PubMed/NCBI

34 

Taube JH, Herschkowitz JI, Komurov K, Zhou AY, Gupta S, Yang J, Hartwell K, Onder TT, Gupta PB, Evans KW, et al: Core epithelial-to-mesenchymal transition interactome gene-expression signature is associated with claudin-low and metaplastic breast cancer subtypes. Proc Natl Acad Sci USA. 107:15449–15454. 2010. View Article : Google Scholar : PubMed/NCBI

35 

Thamilselvan V, Craig DH and Basson MD: FAK association with multiple signal proteins mediates pressure-induced colon cancer cell adhesion via a Src-dependent PI3K/Akt pathway. FASEB J. 21:1730–1741. 2007. View Article : Google Scholar : PubMed/NCBI

36 

Miyazaki T, Karube M, Matsuzaki Y, Ikegami T, Doy M, Tanaka N and Bouscarel B: Taurine inhibits oxidative damage and prevents fibrosis in carbon tetrachloride-induced hepatic fibrosis. J Hepatol. 43:117–125. 2005. View Article : Google Scholar : PubMed/NCBI

37 

Itoh N, Semba S, Ito M, Takeda H, Kawata S and Yamakawa M: Phosphorylation of Akt/PKB is required for suppression of cancer cell apoptosis and tumor progression in human colorectal carcinoma. Cancer. 94:3127–3134. 2002. View Article : Google Scholar : PubMed/NCBI

38 

Tanno S, Tanno S, Mitsuuchi Y, Altomare DA, Xiao GH and Testa JR: AKT activation up-regulates insulin-like growth factor I receptor expression and promotes invasiveness of human pancreatic cancer cells. Cancer Res. 61:589–593. 2001.PubMed/NCBI

39 

Tao C, Lin H and Chen S: The regulation of ERK and p-ERK expression by cisplatin and sorafenib in gastric cancer cells. Gene. 552:106–115. 2014. View Article : Google Scholar : PubMed/NCBI

40 

Ohtsuka S, Ogawa S, Wakamatsu E and Abe R: Cell cycle arrest caused by MEK/ERK signaling is a mechanism for suppressing growth of antigen-hyperstimulated effector T cells. Int Immunol. 28:547–557. 2016. View Article : Google Scholar : PubMed/NCBI

41 

Deer EL, González-Hernández J, Coursen JD, Shea JE, Ngatia J, Scaife CL, Firpo MA and Mulvihill SJ: Phenotype and genotype of pancreatic cancer cell lines. Pancreas. 39:425–435. 2010. View Article : Google Scholar : PubMed/NCBI

42 

Mann KM, Ying H, Juan J, Jenkins NA and Copeland NG: KRAS-related proteins in pancreatic cancer. Pharmacol Ther. 168:29–42. 2016. View Article : Google Scholar : PubMed/NCBI

43 

Larue L and Bellacosa A: Epithelial-mesenchymal transition in development and cancer: Role of phosphatidylinositol 3′ kinase/ AKT pathways. Oncogene. 24:7443–7454. 2005. View Article : Google Scholar : PubMed/NCBI

44 

Liu A, Shao C, Jin G, Liu R, Hao J, Song B, Ouyang L and Hu X: miR-208-induced epithelial to mesenchymal transition of pancreatic cancer cells promotes cell metastasis and invasion. Cell Biochem Biophys. 69:341–346. 2014. View Article : Google Scholar : PubMed/NCBI

45 

Tashiro E, Henmi S, Odake H, Ino S and Imoto M: Involvement of the MEK/ERK pathway in EGF-induced E-cadherin down-regulation. Biochem Biophys Res Commun. 477:801–806. 2016. View Article : Google Scholar : PubMed/NCBI

46 

Iser IC, Pereira MB, Lenz G and Wink MR: The epithelial-to-mesenchymal transition-like process in glioblastoma: An updated systematic review and in silico investigation. Med Res Rev. 37:271–313. 2017. View Article : Google Scholar

47 

Zheng X, Carstens JL, Kim J, Scheible M, Kaye J, Sugimoto H, Wu CC, LeBleu VS and Kalluri R: Epithelial-to-mesenchymal transition is dispensable for metastasis but induces chemoresistance in pancreatic cancer. Nature. 527:525–530. 2015. View Article : Google Scholar : PubMed/NCBI

48 

Arumugam T, Ramachandran V, Fournier KF, Wang H, Marquis L, Abbruzzese JL, Gallick GE, Logsdon CD, McConkey DJ and Choi W: Epithelial to mesenchymal transition contributes to drug resistance in pancreatic cancer. Cancer Res. 69:5820–5828. 2009. View Article : Google Scholar : PubMed/NCBI

Related Articles

Journal Cover

December 2018
Volume 53 Issue 6

Print ISSN: 1019-6439
Online ISSN:1791-2423

Sign up for eToc alerts

Recommend to Library

Copy and paste a formatted citation
APA
Liang, X., Qi, M., Wu, R., Liu, A., Chen, D., Tang, L. ... Shao, C. (2018). Long non-coding RNA CUDR promotes malignant phenotypes in pancreatic ductal adenocarcinoma via activating AKT and ERK signaling pathways. International Journal of Oncology, 53, 2671-2682. https://doi.org/10.3892/ijo.2018.4574
MLA
Liang, X., Qi, M., Wu, R., Liu, A., Chen, D., Tang, L., Chen, J., Hu, X., Li, W., Zhan, L., Shao, C."Long non-coding RNA CUDR promotes malignant phenotypes in pancreatic ductal adenocarcinoma via activating AKT and ERK signaling pathways". International Journal of Oncology 53.6 (2018): 2671-2682.
Chicago
Liang, X., Qi, M., Wu, R., Liu, A., Chen, D., Tang, L., Chen, J., Hu, X., Li, W., Zhan, L., Shao, C."Long non-coding RNA CUDR promotes malignant phenotypes in pancreatic ductal adenocarcinoma via activating AKT and ERK signaling pathways". International Journal of Oncology 53, no. 6 (2018): 2671-2682. https://doi.org/10.3892/ijo.2018.4574