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Article Open Access

Autophagy promotes malignant migration and invasion via miR‑224‑5p/BCL2 in pancreatic mucinous cystadenocarcinoma MCC1 cells

  • Authors:
    • Chengtao Guo
    • Xiaobo Peng
    • Lele Song
    • Mingzhen Ying
    • Yanjun Wu
    • Renxu Chang
    • Jie Li
    • Dan Feng
    • Lixing Zhan
    • Xianbao Zhan
  • View Affiliations / Copyright

    Affiliations: Department of Oncology, Changhai Hospital, The Second Military Medical University, Shanghai 200433, P.R. China, Key Laboratory of Food Safety Research, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, P.R. China
    Copyright: © Guo et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 276
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    Published online on: September 22, 2020
       https://doi.org/10.3892/ol.2020.12139
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Abstract

The prognosis of invasive pancreatic mucinous cystadenocarcinoma (MCC) is poor, and the molecular mechanism underlying its development remains unclear. The present study aimed to explore the potential role of autophagy in pancreatic MCC. The results demonstrated an increase in autophagy signaling in pancreatic MCC tissues and the MCC1 cell line compared with adjacent tissues and normal human pancreatic ductal epithelium (HPDE) cells. In addition, abnormal autophagy activation facilitated the migration and invasion of MCC1 cells. MicroRNA (miR)‑224‑5p expression levels were significantly higher in MCC1 cells compared with those in HPDE cells. Treatment with rapamycin further demonstrated that high levels of autophagy elevated miR‑224‑5p expression in MCC1 cells in a time‑dependent manner. BCL2 was identified as a downstream target gene of miR‑224‑5p, which binds to the 3'‑untranslated region of BCL2. In addition, the results of the present study demonstrated that BCL2 knockdown reversed the inhibition of autophagy mediated by the miR‑224‑5p inhibitor. To the best of our knowledge, this is the first study to evaluate the role of autophagy in pancreatic MCC. Thus, these results suggested that autophagy may be hyperactivated in pancreatic MCC. In addition, the present study identified a positive feedback loop between autophagy signaling and miR‑224‑5p, which may promote the aggressive migration and invasion of MCC1. These results may provide a new insight into the relationship between autophagy and tumor metastasis in pancreatic MCC.
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1 

Farrell JJ: Pancreatic cysts and guidelines. Dig Dis Sci. 62:1827–1839. 2017. View Article : Google Scholar : PubMed/NCBI

2 

Canto MI and Hruban RH: Managing pancreatic cysts: Less is more? Gastroenterology. 148:688–691. 2015. View Article : Google Scholar : PubMed/NCBI

3 

Compagno J and Oertel JE: Mucinous cystic neoplasms of the pancreas with overt and latent malignancy (cystadenocarcinoma and cystadenoma). A clinicopathologic study of 41 cases. Am J Clin Pathol. 69:573–580. 1978. View Article : Google Scholar : PubMed/NCBI

4 

Postlewait LM, Ethun CG, McInnis MR, Merchant N, Parikh A, Idrees K, Isom CA, Hawkins W, Fields RC, Strand M, et al: Association of preoperative risk factors with malignancy in pancreatic mucinous cystic neoplasms: A multicenter study. JAMA Surg. 152:19–25. 2016. View Article : Google Scholar

5 

Sarr MG, Carpenter HA, Prabhakar LP, Orchard TF, Hughes S, van Heerden JA and DiMagno EP: Clinical and pathologic correlation of 84 mucinous cystic neoplasms of the pancreas: Can one reliably differentiate benign from malignant (or premalignant) neoplasms? Ann Surg. 231:205–212. 2000. View Article : Google Scholar : PubMed/NCBI

6 

Del Chiaro M, Verbeke C, Salvia R, Klöppel G, Werner J, McKay C, Friess H, Manfredi R, Van Cutsem E, Löhr M, et al: European experts consensus statement on cystic tumours of the pancreas. Dig Liver Dis. 45:703–711. 2013. View Article : Google Scholar : PubMed/NCBI

7 

Tanaka M, Fernández-del Castillo C, Adsay V, Chari S, Falconi M, Jang JY, Kimura W, Levy P, Pitman MB, Schmidt CM, et al: International consensus guidelines 2012 for the management of IPMN and MCN of the pancreas. Pancreatology. 12:183–197. 2012. View Article : Google Scholar : PubMed/NCBI

8 

Mizushima N: A brief history of autophagy from cell biology to physiology and disease. Nat Cell Biol. 20:521–527. 2018. View Article : Google Scholar : PubMed/NCBI

9 

Kim J, Kundu M, Viollet B and Guan KL: AMPK and mTOR regulate autophagy through direct phosphorylation of ulk1. Nat Cell Biol. 13:132–141. 2011. View Article : Google Scholar : PubMed/NCBI

10 

Levy JM, Towers CG and Thorburn A: Targeting autophagy in cancer. Nat Rev Cancer. 17:528–542. 2017. View Article : Google Scholar : PubMed/NCBI

11 

Dower CM, Wills CA, Frisch SM and Wang HG: Mechanisms and context underlying the role of autophagy in cancer metastasis. Autophagy. 14:1110–1128. 2018. View Article : Google Scholar : PubMed/NCBI

12 

Xu Y, Chang R, Peng Z, Wang Y, Ji W, Guo J, Song L, Dai C, Wei W, Wu Y, et al: Loss of polarity protein AF6 promotes pancreatic cancer metastasis by inducing snail expression. Nat Commun. 26:71842015. View Article : Google Scholar

13 

Chang R, Song L, Xu Y, Wu Y, Dai C, Wang X, Sun X, Hou Y, Li W, Zhan X and Zhan L: Loss of Wwox drives metastasis in triple-negative breast cancer by JAK2/STAT3 axis. Nat Commun. 28:34862018. View Article : Google Scholar

14 

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 : PubMed/NCBI

15 

Xu XD, Song XW, Li Q, Wang GK, Jing Q and Qin YW: Attenuation of microRNA-22 derepressed PTEN to effectively protect rat cardiomyocytes from hypertrophy. J Cell Physiol. 227:1391–1398. 2012. View Article : Google Scholar : PubMed/NCBI

16 

Maes H, Rubio N, Garg AD and Agostinis P: Autophagy: Shaping the tumor microenvironment and therapeutic response. Trends Mol Med. 19:428–446. 2013. View Article : Google Scholar : PubMed/NCBI

17 

He C and Levine B: The beclin 1 interactome. Curr Opin Cell Biol. 22:140–149. 2010. View Article : Google Scholar : PubMed/NCBI

18 

Lock R, Kenific CM, Leidal AM, Salas E and Debnath J: Autophagy-dependent production of secreted factors facilitates oncogenic RAS-driven invasion. Cancer Discov. 4:466–479. 2014. View Article : Google Scholar : PubMed/NCBI

19 

Sharifi MN, Mowers EE, Drake LE, Collier C, Chen H, Zamora M, Mui S and Macleod KF: Autophagy promotes focal adhesion disassembly and cell motility of metastatic tumor cells through the direct interaction of paxillin with LC3. Cell Rep. 15:1660–1672. 2016. View Article : Google Scholar : PubMed/NCBI

20 

Görgülü K, Diakopoulos KN, Ai J, Schoeps B, Kabacaoglu D, Karpathaki AF, Ciecielski KJ, Kaya-Aksoy E, Ruess DA, Berninger A, et al: Levels of the autophagy-related 5 protein affect progression and metastasis of pancreatic tumors in mice. Gastroenterology. 156:203–217. 2019. View Article : Google Scholar : PubMed/NCBI

21 

Diakopoulos KN, Lesina M, Wörmann S, Song L, Aichler M, Schild L, Artati A, Römisch-Margl W, Wartmann T, Fischer R, et al: Impaired autophagy induces chronic atrophic pancreatitis in mice via sex- and nutrition-dependent processes. Gastroenterology. 148:626–638. 2015. View Article : Google Scholar : PubMed/NCBI

22 

Antonucci L, Fagman JB, Kim JY, Todoric J, Gukovsky I, Mackey M, Ellisman MH and Karin M: Basal autophagy maintains pancreatic acinar cell homeostasis and protein synthesis and prevents ER stress. Proc Natl Acad Sci USA. 112:E6166–E6174. 2015. View Article : Google Scholar : PubMed/NCBI

23 

Sun L, Hu L, Cogdell D, Lu L, Gao C, Tian W, Zhang Z, Kang Y, Fleming JB and Zhang W: MIR506 induces autophagy-related cell death in pancreatic cancer cells by targeting the STAT3 pathway. Autophagy. 13:703–714. 2017. View Article : Google Scholar : PubMed/NCBI

24 

Fujii S, Mitsunaga S, Yamazaki M, Hasebe T, Ishii G, Kojima M, Kinoshita T, Ueno T, Esumi H and Ochiai A: Autophagy is activated in pancreatic cancer cells and correlates with poor patient outcome. Cancer Sci. 99:1813–1819. 2008.PubMed/NCBI

25 

Perera RM, Stoykova S, Nicolay BN, Ross KN, Fitamant J, Boukhali M, Lengrand J, Deshpande V, Selig MK, Ferrone CR, et al: Transcriptional control of autophagy-lysosome function drives pancreatic cancer metabolism. Nature. 524:361–365. 2015. View Article : Google Scholar : PubMed/NCBI

26 

Kimmelman AC and White E: Autophagy and tumor metabolism. Cell Metab. 25:1037–1043. 2017. View Article : Google Scholar : PubMed/NCBI

27 

Rybstein MD, Bravo-San Pedro JM, Kroemer G and Galluzzi L: The autophagic network and cancer. Nat Cell Biol. 20:243–251. 2018. View Article : Google Scholar : PubMed/NCBI

28 

Lan SH, Wu SY, Zuchini R, Lin XZ, Su IJ, Tsai TF, Lin YJ, Wu CT and Liu HS: Autophagy suppresses tumorigenesis of hepatitis B virus-associated hepatocellular carcinoma through degradation of microRNA-224. Hepatology. 59:505–517. 2014. View Article : Google Scholar : PubMed/NCBI

29 

Jing Z, Han W, Sui X, Xie J and Pan H: Interaction of autophagy with microRNAs and their potential therapeutic implications in human cancers. Cancer Lett. 356:332–338. 2015. View Article : Google Scholar : PubMed/NCBI

30 

Gibbings D, Mostow S, Jay F, Schwab Y, Cossart P and Voinnet O: Selective autophagy degrades DICER and AGO2 and regulates miRNA activity. Nat Cell Biol. 14:1314–1321. 2012. View Article : Google Scholar : PubMed/NCBI

31 

Zhang B, Guo X, Zhang J, Liu X, Zhan X and Li Z: MicroRNA-224 is downregulated in mucinous cystic neoplasms of the pancreas and may regulate tumorigenesis by targeting jagged1. Mol Med Rep. 10:3303–3309. 2014. View Article : Google Scholar : PubMed/NCBI

32 

Yang S, Wang X, Contino G, Liesa M, Sahin E, Ying H, Bause A, Li Y, Stommel JM, Dell'antonio G, et al: Pancreatic cancers require autophagy for tumor growth. Genes Dev. 25:717–729. 2011. View Article : Google Scholar : PubMed/NCBI

33 

Füllgrabe J, Klionsky DJ and Joseph B: The return of the nucleus: Transcriptional and epigenetic control of autophagy. Nat Rev Mol Cell Biol. 15:65–74. 2014. View Article : Google Scholar : PubMed/NCBI

34 

Li Y, Jiang J, Liu W, Wang H, Zhao L, Liu S, Li P, Zhang S, Sun C, Wu Y, et al: MicroRNA-378 promotes autophagy and inhibits apoptosis in skeletal muscle. Proc Natl Acad Sci USA. 115:E10849–E10858. 2018. View Article : Google Scholar : PubMed/NCBI

35 

Li Z, Wang G, Feng D, Zu G, Li Y, Shi X, Zhao Y, Jing H, Ning S, Le W, et al: Targeting the miR-665-3p-ATG4B-autophagy axis relieves inflammation and apoptosis in intestinal ischemia/reperfusion. Cell Death Dis. 9:483.2018.

36 

Korkmaz G, le Sage C, Tekirdag KA, Agami R and Gozuacik D: MiR-376b controls starvation and mTOR inhibition-related autophagy by targeting ATG4C and BECN1. Autophagy. 8:165–176. 2012. View Article : Google Scholar : PubMed/NCBI

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Copy and paste a formatted citation
Spandidos Publications style
Guo C, Peng X, Song L, Ying M, Wu Y, Chang R, Li J, Feng D, Zhan L, Zhan X, Zhan X, et al: Autophagy promotes malignant migration and invasion via miR‑224‑5p/BCL2 in pancreatic mucinous cystadenocarcinoma MCC1 cells. Oncol Lett 20: 276, 2020.
APA
Guo, C., Peng, X., Song, L., Ying, M., Wu, Y., Chang, R. ... Zhan, X. (2020). Autophagy promotes malignant migration and invasion via miR‑224‑5p/BCL2 in pancreatic mucinous cystadenocarcinoma MCC1 cells. Oncology Letters, 20, 276. https://doi.org/10.3892/ol.2020.12139
MLA
Guo, C., Peng, X., Song, L., Ying, M., Wu, Y., Chang, R., Li, J., Feng, D., Zhan, L., Zhan, X."Autophagy promotes malignant migration and invasion via miR‑224‑5p/BCL2 in pancreatic mucinous cystadenocarcinoma MCC1 cells". Oncology Letters 20.6 (2020): 276.
Chicago
Guo, C., Peng, X., Song, L., Ying, M., Wu, Y., Chang, R., Li, J., Feng, D., Zhan, L., Zhan, X."Autophagy promotes malignant migration and invasion via miR‑224‑5p/BCL2 in pancreatic mucinous cystadenocarcinoma MCC1 cells". Oncology Letters 20, no. 6 (2020): 276. https://doi.org/10.3892/ol.2020.12139
Copy and paste a formatted citation
x
Spandidos Publications style
Guo C, Peng X, Song L, Ying M, Wu Y, Chang R, Li J, Feng D, Zhan L, Zhan X, Zhan X, et al: Autophagy promotes malignant migration and invasion via miR‑224‑5p/BCL2 in pancreatic mucinous cystadenocarcinoma MCC1 cells. Oncol Lett 20: 276, 2020.
APA
Guo, C., Peng, X., Song, L., Ying, M., Wu, Y., Chang, R. ... Zhan, X. (2020). Autophagy promotes malignant migration and invasion via miR‑224‑5p/BCL2 in pancreatic mucinous cystadenocarcinoma MCC1 cells. Oncology Letters, 20, 276. https://doi.org/10.3892/ol.2020.12139
MLA
Guo, C., Peng, X., Song, L., Ying, M., Wu, Y., Chang, R., Li, J., Feng, D., Zhan, L., Zhan, X."Autophagy promotes malignant migration and invasion via miR‑224‑5p/BCL2 in pancreatic mucinous cystadenocarcinoma MCC1 cells". Oncology Letters 20.6 (2020): 276.
Chicago
Guo, C., Peng, X., Song, L., Ying, M., Wu, Y., Chang, R., Li, J., Feng, D., Zhan, L., Zhan, X."Autophagy promotes malignant migration and invasion via miR‑224‑5p/BCL2 in pancreatic mucinous cystadenocarcinoma MCC1 cells". Oncology Letters 20, no. 6 (2020): 276. https://doi.org/10.3892/ol.2020.12139
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