FHL1 inhibits the growth of tongue squamous cell carcinoma cells via G1/S cell cycle arrest

Ren,Wei; Lian,Panfeng; Cheng,Long; Du,Peiyun; Guan,Xin; Wang,Hongyuan; Ding,Lihua; Gao,Zhenyang; Huang,Xin; Xiao,Fengjun; Wang,Lisheng; Bi,Xiaolin; Ye,Qinong; Wang,Enqun

doi:10.3892/mmr.2015.3844

September-2015 Volume 12 Issue 3

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September-2015 Volume 12 Issue 3

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Article

FHL1 inhibits the growth of tongue squamous cell carcinoma cells via G1/S cell cycle arrest

Authors:
- Wei Ren
- Panfeng Lian
- Long Cheng
- Peiyun Du
- Xin Guan
- Hongyuan Wang
- Lihua Ding
- Zhenyang Gao
- Xin Huang
- Fengjun Xiao
- Lisheng Wang
- Xiaolin Bi
- Qinong Ye
- Enqun Wang
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Affiliations: Department of Stomatology, Anqing Municipal Hospital of Anhui Medical University, Anqing, Anhui 246003, P.R. China, Department of Medical Molecular Biology, Beijing Institute of Biotechnology, Beijing 100850, P.R. China, Department of Stomatology, Medical College of Chinese PLA, Beijing 100853, P.R. China, Department of Oral and Maxillofacial Surgery, Beijing Stomatological Hospital, Beijing 100000, P.R. China, Department of Experimental Hematology, Beijing Institute of Radiation Medicine, Beijing 100850, P.R. China, Institute of Cancer Stem Cell, Cancer Center, Dalian Medical University, Dalian, Liaoning 116000, P.R. China
Pages: 3958-3964
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Published online on: May 25, 2015

https://doi.org/10.3892/mmr.2015.3844
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Abstract

Four and a half LIM protein 1 (FHL1) has been characterized as a tumor suppressor in various types of tumor. However, the biological function and underlying mechanism of FHL1 in tongue squamous cell carcinoma (TSCC) remain to be elucidated. The present study demonstrated that FHL1 inhibits anchorage‑dependent and ‑independent growth of TSCC cells in vitro and tumor growth in nude mice, as determined by cell proliferation and soft agar assays. Knockdown of FHL1 with FHL1 small interfering RNA (siRNA) promoted tumor growth in nude mice. Mechanistically, flow cytometric analysis showed that knockdown of FHL1 promoted G1/S cell cycle progression. Furthermore, expression of cell cycle‑associated regulators, cyclin D and cyclin E, were detected by western blotting and reverse transcription‑quantitative polymerase chain reaction. Cyclin D and cyclin E were markedly elevated at both the protein and mRNA level in the FHL1 siRNA‑transfected cells. These results suggested that FHL1 has a tumor suppressive role in TSCC and that FHL1 may be a useful target for TSCC gene therapy.

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1	Parkin DM, Bray F, Ferlay J and Pisani P: Global cancer statistics, 2002. CA Cancer J Clin. 55:74–108. 2005. View Article : Google Scholar : PubMed/NCBI
2	Jemal A, Siegel R, Ward E, Murray T, Xu J and Thun MJ: Cancer statistics, 2007. CA Cancer J Clin. 57:43–66. 2007. View Article : Google Scholar : PubMed/NCBI
3	Heaton CM, Durr ML, Tetsu O, van Zante A and Wang SJ: TP53 and CDKN2a mutations in never-smoker oral tongue squamous cell carcinoma. Laryngoscope. 124:E267–E273. 2014. View Article : Google Scholar : PubMed/NCBI
4	Thavaraj S, Stokes A, Mazuno K, et al: Patients with HPV-related tonsil squamous cell carcinoma rarely harbour oncogenic HPV infection at other pharyngeal sites. Oral Oncol. 50:241–246. 2014. View Article : Google Scholar : PubMed/NCBI
5	Jemal A, Siegel R, Ward E, Hao Y, Xu J and Thun MJ: Cancer statistics, 2009. CA Cancer J Clin. 59:225–249. 2009. View Article : Google Scholar : PubMed/NCBI
6	Matthews JM, Lester K, Joseph S and Curtis DJ: LIM-domain-only proteins in cancer. Nat Rev Cancer. 13:111–122. 2013. View Article : Google Scholar : PubMed/NCBI
7	Cowling BS, Mcgrath MJ, Nguyen MA, et al: Identification of FHL1 as a regulator of skeletal muscle mass: Implications for human myopathy. J Cell Biol. 183:1033–1048. 2008. View Article : Google Scholar : PubMed/NCBI
8	Li X, Jia Z, Shen Y, Ichikawa H, Jarvik J, Nagele RG and Goldberg GS: Coordinate suppression of Sdpr and Fhl1 expression in tumors of the breast, kidney and prostate. Cancer Sci. 99:1326–1333. 2008. View Article : Google Scholar : PubMed/NCBI
9	Ding L, Niu C, Zheng Y, et al: FHL1 interacts with oestrogen receptors and regulates breast cancer cell growth. J Cell Mol Med. 15:72–85. 2011. View Article : Google Scholar
10	Ding L, Wang Z, Yan J, et al: Human four-and-a-half LIM family members suppress tumor cell growth through a TGF-beta-like signaling pathway. J Clin Invest. 119:349–361. 2009.PubMed/NCBI
11	Sakashita K, Mimori K, Tanaka F, et al: Clinical significance of loss of Fhl1 expression in human gastric cancer. Ann Surg Oncol. 15:2293–2300. 2008. View Article : Google Scholar : PubMed/NCBI
12	Niu C, Liang C, Guo J, et al: Downregulation and growth inhibitory role of FHL1 in lung cancer. Int J Cancer. 130:2549–2556. 2012. View Article : Google Scholar
13	Koike K, Kasamatsu A, Iyoda M, et al: High prevalence of epigenetic inactivation of the human four and a half LIM domains 1 gene in human oral cancer. Int J Oncol. 42:141–150. 2013.
14	Cheng L, Li J, Han Y, et al: PES1 promotes breast cancer by differentially regulating ERα and ERβ. J Clin Invest. 122:2857–2870. 2012. View Article : Google Scholar : PubMed/NCBI
15	Cao Z, Xiang J and Li C: Expression of extracellular matrix metalloproteinase inducer and enhancement of the production of matrix metalloproteinase-1 in tongue squamous cell carcinoma. Int J Oral Maxillofac Surg. 38:880–885. 2009. View Article : Google Scholar : PubMed/NCBI
16	Li S, Jiao J, Lu Z and Zhang M: An essential role for N-cadherin and beta-catenin for progression in tongue squamous cell carcinoma and their effect on invasion and metastasis of Tca8113 tongue cancer cells. Oncol Rep. 21:1223–1233. 2009.PubMed/NCBI
17	Malumbres M and Barbacid M: Cell cycle, CDKs and cancer: A changing paradigm. Nat Rev Cancer. 9:153–166. 2009. View Article : Google Scholar : PubMed/NCBI
18	Hochegger H, Takeda S and Hunt T: Cyclin-dependent kinases and cell-cycle transitions: Does one fit all? Nat Rev Mol Cell Biol. 9:910–916. 2008. View Article : Google Scholar : PubMed/NCBI
19	Hanahan D and Weinberg RA: Hallmarks of cancer: The next generation. Cell. 144:646–674. 2011. View Article : Google Scholar : PubMed/NCBI
20	Musgrove EA, Caldon CE, Barraclough J, Stone A and Sutherland RL: Cyclin D as a therapeutic target in cancer. Nat Rev Cancer. 11:558–572. 2011. View Article : Google Scholar : PubMed/NCBI
21	Mahdey HM, Ramanathan A, Ismail SM, Abraham MT, Jamaluddin M and Zain RB: Cyclin D1 amplification in tongue and cheek squamous cell carcinoma. Asian Pac J Cancer Prev. 12:2199–2204. 2011.
22	Rasamny JJ, Allak A, Krook KA, et al: Cyclin D1 and FADD as biomarkers in head and neck squamous cell carcinoma. Otolaryngol Head Neck Surg. 146:923–931. 2012. View Article : Google Scholar : PubMed/NCBI
23	Hwang HC and Clurman BE: Cyclin E in normal and neoplastic cell cycles. Oncogene. 24:2776–2786. 2005. View Article : Google Scholar : PubMed/NCBI
24	Keyomarsi K, Tucker SL, Buchholz TA, et al: Cyclin E and survival in patients with breast cancer. N Engl J Med. 347:1566–1575. 2002. View Article : Google Scholar : PubMed/NCBI
25	Matsumoto M, Kawakami K, Enokida H, et al: CpG hypermeth-ylation of human four-and-a-half LIM domains 1 contributes to migration and invasion activity of human bladder cancer. Int J Mol Med. 26:241–247. 2010.PubMed/NCBI

Journals

International Journal of Molecular Medicine

International Journal of Oncology

Molecular Medicine Reports

Oncology Reports

Experimental and Therapeutic Medicine

Oncology Letters

Biomedical Reports

Molecular and Clinical Oncology

World Academy of Sciences Journal

International Journal of Functional Nutrition

International Journal of Epigenetics

Medicine International

FHL1 inhibits the growth of tongue squamous cell carcinoma cells via G1/S cell cycle arrest

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