CAC1 knockdown reverses drug resistance through the downregulation of P-gp and MRP-1 expression in colorectal cancer
Autoři:
Nanzheng Chen aff001; Ying Kong aff002; Yunhua Wu aff003; Qi Gao aff003; Junke Fu aff001; Xuejun Sun aff003; Qianqian Geng aff004
Působiště autorů:
The thoracic surgery department of the First affiliated hospital of Xi’an Jiaotong University, Xi’an, China
aff001; The general surgery department of the First affiliated hospital of Xi’an Jiaotong University, Xi’an, China
aff002; The medical oncology department of the First affiliated hospital of Xi’an Jiaotong University, Xi’an, China
aff003; The nuclear medicine department of the First affiliated hospital of Xi’an Jiaotong University, Xi’an, China
aff004
Vyšlo v časopise:
PLoS ONE 14(9)
Kategorie:
Research Article
doi:
https://doi.org/10.1371/journal.pone.0222035
Souhrn
CDK2-associated cullin domain 1 (CAC1) is as a novel cell cycle regulator widely expressed in colorectal cancer (CRC). However, its expression and function in drug resistant CRC cells remains elusive. Therefore, the present study aimed to assess the biochemical function and relevance of CAC1 in drug resistant CRC cells, and detect the potential mechanism. For this purpose, a total of 83 CRC cases were collected for the immunohistochemical analysis of CAC1 expression. Functional studies (stable transfection, flow cytometry, colony formation, and invasion and migration assays) were performed in SW480, LoVo and their corresponding 5-FU resistant cells. In addition, a nude mice xenograft model was established for further observation in vivo. In the present study, CAC1 protein expression was higher in CRC tissues than that in normal tissues (P<0.05). Furthermore, CAC1 protein expression was higher in SW480/5-FU cells than in SW480 cells. CAC1 knockdown arrested 5-FU resistant cells at the G1/S phase and increased the sensitivity of 5-FU resistant cells to 5-FU by inducing apoptosis. In addition, CAC1 reduced the invasive and migration ability of SW480/5-FU and LoVo/5-FU cells in vitro, and reduced their tumorigenicity and metastatic ability in vivo. Finally, CAC1 knockdown resulted in decreased P-glycoprotein and MRP-1 protein expression. Based on these results, it can be concluded that CAC1 plays an important role in the occurrence and promotion of drug resistance in CRC. Therefore, the knockdown of CAC1 may be considered as a new strategy for the development of CRC drug resistance treatments in the future.
Klíčová slova:
Medicine and health sciences – Oncology – Cancers and neoplasms – Colorectal cancer – Metastasis – Basic cancer research – Biology and life sciences – Cell biology – Cell processes – Cell death – Apoptosis – Cell cycle and cell division – Molecular biology – Molecular biology techniques – Molecular biology assays and analysis techniques – Gene expression and vector techniques – Protein expression – Biochemistry – Glycobiology – Glycoproteins – P-glycoproteins – Research and analysis methods – Biological cultures – Cell lines – SW480 cells – Animal studies – Experimental organism systems – Model organisms – Mouse models – Animal models
Zdroje
1. Ferlay J, Soerjomataram I, Dikshit R, Eser S, Mathers C, Rebelo M, et al. Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer. 2015;136(5):E359. doi: 10.1002/ijc.29210 25220842
2. NJ S, K C, TM T, L P, K B, D P, et al. Characteristics of Missed or Interval Colorectal Cancer and Patient Survival: A Population-Based Study. Gastroenterology. 2014;146(4):950–60. doi: 10.1053/j.gastro.2014.01.013 24417818
3. Brenner H. Colorectal cancer. Lancet. 2014;383(9927):1490–502. doi: 10.1016/S0140-6736(13)61649-9 24225001
4. Siegel R, DeSantis C, Virgo K, Stein K, Mariotto A, Smith T, et al. Cancer treatment and survivorship statistics, 2012. CA Cancer J Clin. 2012;62(4):220–41. doi: 10.3322/caac.21149 22700443
5. Brenner H, Bouvier AM, Foschi R, Hackl M, Larsen IK, Lemmens V, et al. Progress in colorectal cancer survival in Europe from the late 1980s to the early 21st century: the EUROCARE study. Int J Cancer. 2012;131(7):1649–58. doi: 10.1002/ijc.26192 21607946
6. Sankaranarayanan R, Swaminathan R, Brenner H, Chen K, Chia KS, Chen JG, et al. Cancer survival in Africa, Asia, and Central America: a population-based study. The lancet oncology. 2010;11(2):165–73. doi: 10.1016/S1470-2045(09)70335-3 20005175
7. Boyle T, Keegel T, Bull F, Heyworth J, Fritschi L. Physical activity and risks of proximal and distal colon cancers: a systematic review and meta-analysis. J Natl Cancer Inst. 2012:djs354.
8. Aune D, Lau R, Chan DS, Vieira R, Greenwood DC, Kampman E, et al. Nonlinear reduction in risk for colorectal cancer by fruit and vegetable intake based on meta-analysis of prospective studies. Gastroenterology. 2011;141(1):106–18. doi: 10.1053/j.gastro.2011.04.013 21600207
9. Elmunzer BJ, Hayward RA, Schoenfeld PS, Saini SD, Deshpande A, Waljee AK. Effect of flexible sigmoidoscopy-based screening on incidence and mortality of colorectal cancer: a systematic review and meta-analysis of randomized controlled trials. PLoS Med. 2012;9(12):e1001352. doi: 10.1371/journal.pmed.1001352 23226108
10. Liu Y, Wu W, Hong W, Sun X, Wu J, Huang Q. Raltitrexed-based chemotherapy for advanced colorectal cancer. Clin Res Hepatol Gastroenterol. 2014;38(2):219–25. doi: 10.1016/j.clinre.2013.11.006 24388340
11. Kong Y, Kejun N, Yin Y. Identification and characterization of CAC1 as a novel CDK2-associated cullin. Cell Cycle. 2009;8(21):3552–61. doi: 10.4161/cc.8.21.9955 19829063
12. Kigoshi Y, Fukuda T, Endo T, Hayasaka N, Iemura S-i, Natsume T, et al. CACUL1/CAC1 Regulates the Antioxidant Response by Stabilizing Nrf2. Sci Rep. 2015;5.
13. Hummel R, Wang T, Watson DI, Michael MZ, Van der Hoek M, Haier J, et al. Chemotherapy-induced modification of microRNA expression in esophageal cancer. Oncol Rep. 2011;26(4):1011. doi: 10.3892/or.2011.1381 21743970
14. Han Y, Haraguchi T, Iwanaga S, Tomotake H, Okazaki Y, Mineo S, et al. Consumption of some polyphenols reduces fecal deoxycholic acid and lithocholic acid, the secondary bile acids of risk factors of colon cancer. J Agric Food Chem. 2009;57(18):8587–90. doi: 10.1021/jf900393k 19711910
15. Moon M, Um S-J, Kim E-J. CAC1 negatively regulates RARα activity through cooperation with HDAC. Biochem Biophys Res Commun. 2012;427(1):41–6. doi: 10.1016/j.bbrc.2012.08.142 22982681
16. Kim J, Park U-H, Moon M, Um S-J, Kim E-J. Negative regulation of ERα by a novel protein CAC1 through association with histone demethylase LSD1. FEBS Lett. 2013;587(1):17–22. doi: 10.1016/j.febslet.2012.10.054 23178685
17. Kong Y, Bai P-s, Sun H, Nan K-j. Expression of the newly identified gene CAC1 in the hippocampus of Alzheimer’s disease patients. J Mol Neurosci. 2012;47(2):207–18. doi: 10.1007/s12031-012-9717-5 22415352
18. Guo XX, Goessl E, Jin G, Collie-Duguid ES, Cassidy J, Wang WG, et al. Cell cycle perturbation and acquired 5-Fluorouracil chemoresistance. Anticancer Res, 2008; 28:9–14. 18383818
19. Kaliszczak M, Patel H, Kroll SHB, Carroll L, Smith G, Delaney S, et al. Development of a cycin-dependent kinase inhibitor devoid of ABC transporter-dependent drug resistance. British J of Cancer, 2013; 109:2356–2367
20. Greene FL. Current TNM staging of colorectal cancer. The Lancet Oncology. 2007;8(7):572–3. doi: 10.1016/S1470-2045(07)70185-7 17613421
21. Yin H, Xu L, Yao H. New opinions of colorectal cancer in 2010. Chin J Practical Surg. 2010;30:764–8.
22. Chen TJ, Gao F, Yang T, Thakur A, Ren H, Li Y, et al. CDK-associated Cullin 1 promotes cell proliferation with activation of ERK1/2 in human lung cancer A549 cells. Biochem Biophys Res Commun. 2013;437(1):108–13. doi: 10.1016/j.bbrc.2013.06.048 23806693
23. Zheng Q, Zhao L-Y, Kong Y, Nan K-J, Yao Y, Liao Z-J. CDK-associated Cullin 1 can promote cell proliferation and inhibit cisplatin-induced apoptosis in the AGS gastric cancer cell line. World J Surg Oncol. 2013;11(1):5.
24. Kong Y, Bai P-s, Sun H, Nan K-j, Chen N-z, Qi X-g. The deoxycholic acid targets miRNA-dependent CAC1 gene expression in multidrug resistance of human colorectal cancer. The international journal of biochemistry & cell biology. 2012;44(12):2321–32.
25. Zhang Y-s, Shen Q, Li J. Traditional Chinese medicine targeting apoptotic mechanisms for esophageal cancer therapy. Acta Pharmacol Sin. 2015.
26. Petaccia M, Gentili P, Bešker N, D'Abramo M, Giansanti L, Leonelli F, et al. Kinetics and mechanistic study of competitive inhibition of thymidine phosphorylase by 5-fluoruracil derivatives. Colloids Surf B Biointerfaces. 2016;140:121–7. doi: 10.1016/j.colsurfb.2015.12.020 26752208
27. Li Q, Wang X, Shen A, Zhang Y, Chen Y, Sferra TJ, et al. Hedyotis diffusa Willd overcomes 5-fluorouracil resistance in human colorectal cancer HCT-8/5-FU cells by downregulating the expression of P-glycoprotein and ATP-binding casette subfamily G member 2. Exp Ther Med. 2015;10(5):1845–50. doi: 10.3892/etm.2015.2762 26640560
28. Kong Y, Ma L-q, Bai P-s, Da R, Sun H, Qi X-g, et al. Helicobacter pylori promotes invasion and metastasis of gastric cancer cells through activation of AP-1 and up-regulation of CACUL1. The international journal of biochemistry & cell biology. 2013;45(11):2666–78.
29. Zhang L, Dong Y, Zhu N, Tsoi H, Zhao Z, Wu CW, et al. microRNA-139-5p exerts tumor suppressor function by targeting NOTCH1 in colorectal cancer. Mol Cancer. 2014;13(1):124.
30. Shen K, Mao R, Ma L, Li Y, Qiu Y, Cui D, et al. Post‐transcriptional regulation of the tumor suppressor miR‐139‐5p and a network of miR‐139‐5p‐mediated mRNA interactions in colorectal cancer. FEBS J. 2014;281(16):3609–24. doi: 10.1111/febs.12880 24942287
Článek vyšel v časopise
PLOS One
2019 Číslo 9
- S diagnostikou Parkinsonovy nemoci může nově pomoci AI nástroj pro hodnocení mrkacího reflexu
- Je libo čepici místo mozkového implantátu?
- Pomůže v budoucnu s triáží na pohotovostech umělá inteligence?
- AI může chirurgům poskytnout cenná data i zpětnou vazbu v reálném čase
- Nová metoda odlišení nádorové tkáně může zpřesnit resekci glioblastomů
Nejčtenější v tomto čísle
- Graviola (Annona muricata) attenuates behavioural alterations and testicular oxidative stress induced by streptozotocin in diabetic rats
- CH(II), a cerebroprotein hydrolysate, exhibits potential neuro-protective effect on Alzheimer’s disease
- Comparison between Aptima Assays (Hologic) and the Allplex STI Essential Assay (Seegene) for the diagnosis of Sexually transmitted infections
- Assessment of glucose-6-phosphate dehydrogenase activity using CareStart G6PD rapid diagnostic test and associated genetic variants in Plasmodium vivax malaria endemic setting in Mauritania
Zvyšte si kvalifikaci online z pohodlí domova
Všechny kurzy