Downregulation of microRNA‑449a‑5p promotes esophageal squamous cell carcinoma cell proliferation via cyclin D1 regulation

Jiang,Tao; Liu,Junfeng; Mu,Jixing

doi:10.3892/mmr.2018.9030

Downregulation of microRNA‑449a‑5p promotes esophageal squamous cell carcinoma cell proliferation via cyclin D1 regulation

Authors:
- Tao Jiang
- Junfeng Liu
- Jixing Mu
View Affiliations

Affiliations: Department of Thoracic Surgery, Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei 050011, P.R. China, First Hospital of Xingtai, Xingtai, Hebei 054000, P.R. China
Published online on: May 17, 2018 https://doi.org/10.3892/mmr.2018.9030
Pages: 848-854
Copyright: © Jiang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Aberrant microRNA-449a (miR-449a-5p) expression has been demonstrated to be associated with the development of various cancer types. However, the effect of miR‑449a‑5p on esophageal squamous cell carcinoma (ESCC) cell proliferation remains unknown. The present study aimed to determine whether miR‑449a‑5p may regulate ESCC cell proliferation via negative regulation of cyclin D1. Reverse transcription quantitative‑polymerase chain reaction was used to measure the expression of miR‑449a‑5p in ESCC tissues and cells. Western blot was performed to analyze the protein level of cyclin D1. The proliferation of ESCC cells was determined by MTT and clone formation assay. Paired ESCC and adjacent normal esophageal squamous tissues were collected from patients with ESCC. It was demonstrated that miR‑449a‑5p expression was reduced, whereas cyclin D1 expression was increased in ESCC tissues compared with adjacent normal tissues. Proliferation was investigated in vivo using the ESCC cell line Eca‑190. miR‑449a‑5p inhibitor transfection facilitated the proliferation of Eca‑109 cells. By contrast, transfection with miR‑449a‑5p mimics inhibited Eca‑109 cell proliferation. Furthermore, it was confirmed that miR‑449a‑5p directly bound to the 3'‑untranslated region of cyclin D1. Transfection with cyclin D1 small interfering RNA reversed the effects of the miR‑449a‑5p inhibitor on Eca‑109 cell proliferation. In conclusion, miR‑449a‑5p may control ESCC proliferation through the negative regulation of cyclin D1 expression.

View Figures

View References

1	Ferlay J, Shin HR, Bray F, Forman D, Mathers C and Parkin DM: Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int J Cancer. 127:2893–2917. 2010. View Article : Google Scholar : PubMed/NCBI
2	Otsubo T, Yamada K, Hagiwara T, Oshima K, Iida K, Nishikata K, Toyoda T, Igari T, Nohara K, Yamashita S, et al: DNA hypermethyation and silencing of PITX1 correlated with advanced stage and poor postoperative prognosis of esophageal squamous cell carcinoma. Oncotarget. 8:84434–84448. 2017. View Article : Google Scholar : PubMed/NCBI
3	Shaheen O, Ghibour A and Alsaid B: Esophageal cancer metastases to unexpected site: A systematic review. Gastroenterol Res Pract. 2017:16573102017. View Article : Google Scholar : PubMed/NCBI
4	Luo Y, Mao Q, Wang X, Yu J and Li M: Radiotherapy for esophageal carcinoma: Dose, response and survival. Cancer Manag Res. 10:13–21. 2017. View Article : Google Scholar : PubMed/NCBI
5	Wu SG, Zhang WW, He ZY, Sun JY, Chen YX and Guo L: Sites of metastasis and overall survival in esophageal cancer: A population-based study. Cancer Manag Res. 9:781–788. 2017. View Article : Google Scholar : PubMed/NCBI
6	Pennathur A, Gibson MK, Jobe BA and Luketich JD: Oesophageal carcinoma. Lancet. 381:400–412. 2013. View Article : Google Scholar : PubMed/NCBI
7	Harada K, Baba Y, Ishimoto T, Shigaki H, Kosumi K, Yoshida N, Watanabe M and Baba H: The role of microRNA in esophageal squamous cell carcinoma. J Gastroenterol. 51:520–530. 2016. View Article : Google Scholar : PubMed/NCBI
8	Wan TM, Lam CS, Nq L, Chow AK, Wong SK, Li HS, Man JH, Lo OS, Foo D, Cheung A, et al: The clinicopathological significance of miR-133a in colorectal cancer. Dis Markers. 2014:9192832014. View Article : Google Scholar : PubMed/NCBI
9	He L and Hannon GJ: MicroRNAs: Small RNAs with a big role gene regulation. Nat Rev Genet. 5:522–531. 2004. View Article : Google Scholar : PubMed/NCBI
10	Schickel R, Boyerinas B, Park SM and Peter ME: MicroRNAs: Key players in the immune system, differentiation, tumorigenesis and cell death. Oncogene. 27:5959–5974. 2008. View Article : Google Scholar : PubMed/NCBI
11	El-Daly SM, Abba ML and Gamal-Eldeen AM: The role of microRNAs in photodynmic therapy of cancer. Eur J Med Chem. 142:550–555. 2017. View Article : Google Scholar : PubMed/NCBI
12	Zhao L, Shan B, Du Y, Wang M, Liu L and Ren FZ: Periplocin from Cortex periplocae inhibits cell growth and down-regulates survivin and c-myc expression in colon cancer in vitro and in vivo via beta-catenin/TCF signaling. Oncol Rep. 24:375–383. 2010.PubMed/NCBI
13	Yong-Ming H, Ai-Jun J, Xiao-Yue X, Jian-Wei L, Chen Y and Ye C: miR-449a: A potential therapeutic agent for cancer. Anticancer Drugs. 28:1067–1078. 2017. View Article : Google Scholar : PubMed/NCBI
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	Liu JF, Wang QZ and Hou J: Surgical treatment for cancer of the esophagus and gastric cardia in Hebei, China. Br J Surg. 91:90–98. 2004. View Article : Google Scholar : PubMed/NCBI
16	Stoner GD and Wang LS: Chemoprevention of esophageal squamous cell carcinoma with berries. Top Curr Chem. 329:1–20. 2013. View Article : Google Scholar : PubMed/NCBI
17	Siegel R, Naishadham D and Jemal A: Cancer statistics, 2013. CA Cancer J Clin. 63:11–30. 2013. View Article : Google Scholar : PubMed/NCBI
18	Mei LL, Qiu YT, Zhang B and Shi ZZ: MicroRNAs in esophageal squamous cell carcinoma: Potential biomarkers and therapeutic targets. Cancer Biomark. 19:1–9. 2017. View Article : Google Scholar : PubMed/NCBI
19	Wei W, Hu Z, Fu H, Tie Y, Zhang H, Wu Y and Zheng X: MicroRNA-1 and microRNA-499 downregulate the expression of the ets1 proto-oncogene in HepG2 cells. Oncol Rep. 28:701–706. 2012. View Article : Google Scholar : PubMed/NCBI
20	Voorhoeve PM, le Sage C, Schrier M, Gillis AJ, Stoop H, Nagel R, Liu YP, van Duijse J, Drost J, Griekspoor A, et al: A genetic screen implicates miRNA-372 and miRNA-373 as oncogenes in testicular germ cell tumors. Cell. 124:1169–1181. 2006. View Article : Google Scholar : PubMed/NCBI
21	Detassis S, Grasso M, Del Vescovo V and Denti MA: MicroRNAs make the call in cancer personalized medicine. Front Cell Dev Biol. 5:862017. View Article : Google Scholar : PubMed/NCBI
22	Johnson SM, Grosshans H, Shingara J, Byrom M, Jarvis R, Cheng A, Labourier E, Reinert KL, Brown D and Slack FJ: RAS is regulated by the let-7 microRNA family. Cell. 120:635–647. 2005. View Article : Google Scholar : PubMed/NCBI
23	Calin GA, Sevignani C, Dumitru CD, Hyslop T, Noch E, Yendamuri S, Shimizu M, Rattan S, Bullrich F, Negrini M and Croce CM: Human microRNA genes are frequently located at fragile sites and genomic regions involved in cancers. Proc Natl Acad Sci USA. 101:2999–3004. 2004. View Article : Google Scholar : PubMed/NCBI
24	O'Donnell KA, Wentzel EA, Zeller KI, Dang CV and Mendell JT: C-Myc regulated microRNAs modulate E2F1 expression. Nature. 435:839–843. 2005. View Article : Google Scholar : PubMed/NCBI
25	Langevin SM and Christensen BC: Let-7 microRNA-binding-site polymorphism in the 3′UTR of KRAS and colorectal cancer outcome: A systematic review and meta-analysis. Cancer Med. 3:1385–1395. 2014. View Article : Google Scholar : PubMed/NCBI
26	Pekarsky Y, Balatti V and Croce CM: BCL2 and miR-15/16: From gene discovery to treatment. Cell Death Differ. 25:21–26. 2018. View Article : Google Scholar : PubMed/NCBI
27	Noonan EJ, Place RF, Pookot D, Basak S, Whitson JM, Hirata H, Giardina C and Dahiya R: miR-449a targets HDAC-1 and induces growth arrest in prostate cancer. Oncogene. 28:1714–1724. 2009. View Article : Google Scholar : PubMed/NCBI
28	Kheir Bou T, Futoma-Kazmierczak E, Jacobsen A, Krogh A, Bardram L, Hother C, Grønbæk K, Federspiel B, Lund AH and Friis-Hansen L: miR-449 inhibits cell proliferation and is down-regulated in gastric cancer. Mol Cancer. 10:292011. View Article : Google Scholar : PubMed/NCBI
29	Chen H, Lin YW, Mao YQ, Wu J, Liu YF, Zheng XY and Xie LP: MicroRNA-449a acts as a tumor suppressor in human bladder cancer through the regulation of pocket proteins. Cancer Lett. 320:40–47. 2012. View Article : Google Scholar : PubMed/NCBI
30	Jeon HS, Lee SY, Lee EJ, Yun SC, Cha EJ, Choi E, Na MJ, Park JY, Kang J and Son JW: Combining microRNA-449a/b with a HDAC inhibitor has a synergistic effect on growth arrest in lung cancer. Lung Cancer. 76:171–176. 2012. View Article : Google Scholar : PubMed/NCBI
31	Yang X, Feng M, Jiang X, Wu Z, Li Z, Aau M and Yu Q: MiR-449a and miR-449b are direct transcriptional targets of E2F1 and negatively regulate pRb-E2F1 activity through a feedback loop by targeting CDK6 and CDC25A. Genes Dev. 23:2388–2393. 2009. View Article : Google Scholar : PubMed/NCBI
32	Lizé M, Pilarski S and Dobbelstein M: E2F1-inducible microRNA 449a/b suppresses cell proliferation and promotes apoptosis. Cell Death Differ. 17:452–458. 2010. View Article : Google Scholar : PubMed/NCBI
33	Feng M and Yu Q: miR-449 regulates CDK-Rb-E2F1 through an auto-regulatory feedback circuit. Cell Cycle. 9:213–214. 2010. View Article : Google Scholar : PubMed/NCBI
34	Noonan EJ, Place RF, Basak S, Pookot D and Li LC: miR-449a causes Rb-dependent cell cycle arrest and senescence in prostate cancer cells. Oncotarget. 1:349–358. 2010.PubMed/NCBI
35	Ni Y, Meng L, Wang L, Dong W, Shen H, Wang G, Liu Q and Du J: MicroRNA-143 functions as a tumor suppressor in human esophageal squamous cell carcinoma. Gene. 517:197–204. 2013. View Article : Google Scholar : PubMed/NCBI
36	Felekkis K, Touvana E, Stefanou Ch and Deltas C: microRNAs: A newly described class of encoded molecules that play a role in health and disease. Hippokratia. 14:236–240. 2010.PubMed/NCBI