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Article

HMGB1 knockdown effectively inhibits the progression of rectal cancer by suppressing HMGB1 expression and promoting apoptosis of rectal cancer cells

  • Authors:
    • Zhiwei Wang
    • Xiaoyan Wang
    • Jiantian Li
    • Cheng Yang
    • Zhiyuan Xing
    • Ruiyun Chen
    • Fei Xu
  • View Affiliations / Copyright

    Affiliations: Qingdao Medical College, Qingdao University, Qingdao, Shandong 266042, P.R. China, Healthcare Ward, Qingdao Central Medical Group, Qingdao, Shandong 266042, P.R. China, Department of Gastrointestinal and Anorectal Surgery, Qingdao Central Medical Group, Qingdao, Shandong 266042, P.R. China
  • Pages: 1026-1032
    |
    Published online on: May 24, 2016
       https://doi.org/10.3892/mmr.2016.5340
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Abstract

Rectal cancer is a malignant gastrointestinal tumor, which is associated with high morbidity and mortality. High‑mobility group protein 1 (HMGB1) is widely present in the nucleus of eukaryotic cells, and is highly conserved between humans and rodents. Recently, HMGB1 has been reported to be involved in the progression and metastasis of human cancer; however, its role in the development and metastasis of human rectal cancer remains unclear. The present study detected the expression levels of HMGB1 in pathological specimens from patients with clinically identified rectal cancer using immunohistochemistry and western blotting. The results demonstrated that HMGB1 was highly expressed in samples from patients with rectal cancer. The positive rate of HMGB1 in rectal cancer tissues was 96.08% (49/51), which was significantly higher compared with 3.92% (2/51) in normal tissues. In addition, western blotting indicated that HMGB1 was distributed and located not only in the nucleus, but also in the cytoplasm of colorectal cancer cells. HMGB1‑specific short hairpin (sh)RNA was used to silence the endogenous expression of HMGB1 in colorectal cancer cells. A functional assay demonstrated that knockdown of endogenous HMGB1 expression significantly inhibited the proliferation of SW620 and Colo320 cells. Furthermore, western blotting revealed that knockdown of endogenous HMGB1 expression contributed to activation of caspase‑3 and the substrate poly (ADP‑ribose) polymerase. The expression levels of B‑cell lymphoma 2 (Bcl‑2) and Bcl‑2‑associated X protein (Bax) were also detected by western blotting. As expected, decreased levels of Bcl‑2 and increased levels of Bax were detected in the HMGB1 shRNA‑transfected colorectal cancer cells, and the Bax/Bcl‑2 ratio was increased in HMGB1 shRNA‑transfected cells. These data indicated that HMGB1 may act as an oncogene in rectal cancer, and knockdown of endogenous HMGB1 expression may significantly inhibit the proliferation of colorectal cancer cells and promote apoptosis of tumor cells. Further research regarding the mechanisms underlying the effects of HMGB1 on the progression of rectal cancer may provide novel targets for the treatment of rectal cancer, and provide a theoretical reference for clinical treatment.
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1 

Yaffee P, Osipov A, Tan C, Tuli R and Hendifar A: Review of systemic therapies for locally advanced and metastatic rectal cancer. J Gastrointest Oncol. 6:185–200. 2015.PubMed/NCBI

2 

Harji DP, Griffiths B, Velikova G, Sagar PM and Brown J: Systematic review of health-related quality of life issues in locally recurrent rectal cancer. J Surg Oncol. 111:431–438. 2015. View Article : Google Scholar : PubMed/NCBI

3 

Poulsen LØ, Qvortrup C, Pfeiffer P, Yilmaz M, Falkmer U and Sorbye H: Review on adjuvant chemotherapy for rectal cancer - why do treatment guidelines differ so much? Acta Oncol. 54:437–446. 2015. View Article : Google Scholar : PubMed/NCBI

4 

Arezzo A, Passera R, Salvai A, Arolfo S, Allaix ME, Schwarzer G and Morino M: Laparoscopy for rectal cancer is oncologically adequate: A systematic review and meta-analysis of the literature. Surg Endosc. 29:334–348. 2015. View Article : Google Scholar

5 

Nussbaum N and Altomare I: The neoadjuvant treatment of rectal cancer: A review. Curr Oncol Rep. 17:4342015. View Article : Google Scholar : PubMed/NCBI

6 

Ghouti L, Pereira P, Filleron T, Humeau M, Guimbaud R, Selves J and Carrere N: Pelvic exenterations for specific extraluminal recurrences in the era of total mesorectal excision: Is there still a chance for cure? A single-center review of patients with extraluminal pelvic recurrence for rectal cancer from March 2004 to November 2010. Am J Surg. 209:352–362. 2015. View Article : Google Scholar

7 

Guren MG, Undseth C, Rekstad BL, Brændengen M, Dueland S, Spindler KL, Glynne-Jones R and Tveit KM: Reirradiation of locally recurrent rectal cancer: A systematic review. Radiother Oncol. 113:151–157. 2014. View Article : Google Scholar

8 

Lotze MT and DeMarco RA: Dealing with death: HMGB1 as a novel target for cancer therapy. Curr Opin Investig Drugs. 4:1405–1409. 2003.

9 

Süren D, Yildirim M, Demirpençe Ö, Kaya V, Alikanoğlu AS, Bülbüller N, Yıldız M and Sezer C: The role of high mobility group box 1 (HMGB1) in colorectal cancer. Med Sci Monit. 20:530–537. 2014. View Article : Google Scholar : PubMed/NCBI

10 

Flohr AM, Rogalla P, Meiboom M, Borrmann L, Krohn M, Thode-Halle B and Bullerdiek J: Variation of HMGB1 expression in breast cancer. Anticancer Res. 21:3881–3885. 2001.

11 

Jiao Y, Wang HC and Fan SJ: Growth suppression and radiosensitivity increase by HMGB1 in breast cancer. Acta Pharmacol Sin. 28:1957–1967. 2007. View Article : Google Scholar : PubMed/NCBI

12 

Ohmori H, Luo Y and Kuniyasu H: Non-histone nuclear factor HMGB1 as a therapeutic target in colorectal cancer. Expert Opin Ther Targets. 15:183–193. 2011. View Article : Google Scholar : PubMed/NCBI

13 

Moriwaka Y, Luo Y, Ohmori H, Fujii K, Tatsumoto N, Sasahira T and Kuniyasu H: HMGB1 attenuates anti-metastatic defense of the lymph nodes in colorectal cancer. Pathobiology. 77:17–23. 2010. View Article : Google Scholar : PubMed/NCBI

14 

Wang C, Fei G, Liu Z, Li Q, Xu Z and Ren T: HMGB1 was a pivotal synergistic effecor for CpG oligonucleotide to enhance the progression of human lung cancer cells. Cancer Biol Ther. 13:727–736. 2012. View Article : Google Scholar : PubMed/NCBI

15 

Liu Y, Zhang P, Wu Z, Chen J and Zhou Q: Screening of highly-expressed-HMGB1-gene human lung cancer cell lines. Zhongguo Fei Ai Za Zhi. 12:965–968. 2009.In Chinese.

16 

Yang GL, Zhang LH, Bo JJ, Huo XJ, Chen HG, Cao M, Liu DM and Huang YR: Increased expression of HMGB1 is associated with poor prognosis in human bladder cancer. J Surg Oncol. 106:57–61. 2012. View Article : Google Scholar : PubMed/NCBI

17 

Chen J, Liu X, Zhang J and Zhao Y: Targeting HMGB1 inhibits ovarian cancer growth and metastasis by lentivirus-mediated RNA interference. J Cell Physiol. 227:3629–3638. 2012. View Article : Google Scholar : PubMed/NCBI

18 

Song B, Song WG, Li ZJ, Xu ZF, Wang XW, Wang CX and Liu J: Effect of HMGB1 silencing on cell proliferation, invasion and apoptosis of MGC-803 gastric cancer cells. Cell Biochem Funct. 30:11–17. 2012. View Article : Google Scholar

19 

Zhang J, Liu C and Hou R: Knockdown of HMGB1 improves apoptosis and suppresses proliferation and invasion of glioma cells. Chin J Cancer Res. 26:658–668. 2014.

20 

Gong W, Wang ZY, Chen GX, Liu YQ, Gu XY and Liu WW: Invasion potential of H22 hepatocarcinoma cells is increased by HMGB1-induced tumor NF-κB signaling via initiation of HSP70. Oncol Rep. 30:1249–1256. 2013.PubMed/NCBI

21 

Zhang J, Kou YB, Zhu JS, Chen WX and Li S: Knockdown of HMGB1 inhibits growth and invasion of gastric cancer cells through the NF-κB pathway in vitro and in vivo. Int J Oncol. 44:1268–1276. 2014.PubMed/NCBI

22 

Sims GP, Rowe DC, Rietdijk ST, Herbst R and Coyle AJ: HMGB1 and RAGE in inflammation and cancer. Annu Rev Immunol. 28:367–388. 2010. View Article : Google Scholar : PubMed/NCBI

23 

Tang D, Loze MT, Zeh HJ and Kang R: The redox protein HMGB1 regulates cell death and survival in cancer treatment. Autophagy. 6:1181–1183. 2010. View Article : Google Scholar : PubMed/NCBI

24 

Chang BP, Wang DS, Xing JW, Yang SH, Chu Q and Yu SY: MiR-200c inhibits metastasis of breast cancer cells by targeting HMGB1. J Huazhong Univ Sci Technolog Med Sci. 34:201–206. 2014. View Article : Google Scholar : PubMed/NCBI

25 

Liu W, Zhang Z, Zhang Y, Chen X, Guo S, Lei Y, Xu Y, Ji C, Bi Z and Wang K: HMGB1-mediated autophagy modulates sensitivity of colorectal cancer cells to oxaliplatin via MEK/ERK signaling pathway. Cancer Biol Ther. 16:511–517. 2015. View Article : Google Scholar : PubMed/NCBI

26 

Zhang J, Zhang R, Lu WW, Zhu JS, Xia LQ, Lu YM and Chen NW: Clinical significance of hmgb1 expression in human gastric cancer. Int J Immunopathol Pharmacol. 27:543–551. 2014.

27 

Li ZJ, Song B, Liu J, Han JJ, Wang CX, Zhu YX and Xu ZF: Inhibitory effect of silencing of HMGB1 gene expression on the invasive and metastatic abilities of MGC-803 gastric cancer cells. Zhonghua Zhong Liu Za Zhi. 35:244–248. 2013.In Chinese. PubMed/NCBI

28 

Zhang J, Zhu JS, Zhou Z, Chen WX and Chen NW: Inhibitory effects of ethyl pyruvate administration on human gastric cancer growth via regulation of the HMGB1-RAGE and Akt pathways in vitro and in vivo. Oncol Rep. 27:1511–1519. 2012.PubMed/NCBI

29 

Zhang X, Wang H and Wang J: Expression of HMGB1 and NF-κB p65 and its significance in non-small cell lung cancer. Contemp Oncol (Pozn). 17:350–355. 2013.

30 

Wittwer C, Boeck S, Heinemann V, Haas M, Stieber P, Nagel D and Holdenrieder S: Circulating nucleosomes and immunogenic cell death markers HMGB1, sRAGE and DNAse in patients with advanced pancreatic cancer undergoing chemotherapy. Int J Cancer. 133:2619–2630. 2013.PubMed/NCBI

31 

Wild CA, Brandau S, Lotfi R, Mattheis S, Gu X, Lang S and Bergmann C: HMGB1 is overexpressed in tumor cells and promotes activity of regulatory T cells in patients with head and neck cancer. Oral Oncol. 48:409–416. 2012. View Article : Google Scholar : PubMed/NCBI

32 

Li ML, Wang XF, Tan ZJ, Dong P, Gu J, Lu JH, Wu XS, Zhang L, Ding QC, Wu WG, et al: Ethyl pyruvate administration suppresses growth and invasion of gallbladder cancer cells via downregulation of HMGB1-RAGE axis. Int J Immunopathol Pharmacol. 25:955–965. 2012.

33 

Livesey KM, Kang R, Zeh HJ III, Lotze MT and Tang D: Direct molecular interactions between HMGB1 and TP53 in colorectal cancer. Autophagy. 8:846–848. 2012. View Article : Google Scholar : PubMed/NCBI

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Copy and paste a formatted citation
Spandidos Publications style
Wang Z, Wang X, Li J, Yang C, Xing Z, Chen R and Xu F: HMGB1 knockdown effectively inhibits the progression of rectal cancer by suppressing HMGB1 expression and promoting apoptosis of rectal cancer cells. Mol Med Rep 14: 1026-1032, 2016.
APA
Wang, Z., Wang, X., Li, J., Yang, C., Xing, Z., Chen, R., & Xu, F. (2016). HMGB1 knockdown effectively inhibits the progression of rectal cancer by suppressing HMGB1 expression and promoting apoptosis of rectal cancer cells. Molecular Medicine Reports, 14, 1026-1032. https://doi.org/10.3892/mmr.2016.5340
MLA
Wang, Z., Wang, X., Li, J., Yang, C., Xing, Z., Chen, R., Xu, F."HMGB1 knockdown effectively inhibits the progression of rectal cancer by suppressing HMGB1 expression and promoting apoptosis of rectal cancer cells". Molecular Medicine Reports 14.1 (2016): 1026-1032.
Chicago
Wang, Z., Wang, X., Li, J., Yang, C., Xing, Z., Chen, R., Xu, F."HMGB1 knockdown effectively inhibits the progression of rectal cancer by suppressing HMGB1 expression and promoting apoptosis of rectal cancer cells". Molecular Medicine Reports 14, no. 1 (2016): 1026-1032. https://doi.org/10.3892/mmr.2016.5340
Copy and paste a formatted citation
x
Spandidos Publications style
Wang Z, Wang X, Li J, Yang C, Xing Z, Chen R and Xu F: HMGB1 knockdown effectively inhibits the progression of rectal cancer by suppressing HMGB1 expression and promoting apoptosis of rectal cancer cells. Mol Med Rep 14: 1026-1032, 2016.
APA
Wang, Z., Wang, X., Li, J., Yang, C., Xing, Z., Chen, R., & Xu, F. (2016). HMGB1 knockdown effectively inhibits the progression of rectal cancer by suppressing HMGB1 expression and promoting apoptosis of rectal cancer cells. Molecular Medicine Reports, 14, 1026-1032. https://doi.org/10.3892/mmr.2016.5340
MLA
Wang, Z., Wang, X., Li, J., Yang, C., Xing, Z., Chen, R., Xu, F."HMGB1 knockdown effectively inhibits the progression of rectal cancer by suppressing HMGB1 expression and promoting apoptosis of rectal cancer cells". Molecular Medicine Reports 14.1 (2016): 1026-1032.
Chicago
Wang, Z., Wang, X., Li, J., Yang, C., Xing, Z., Chen, R., Xu, F."HMGB1 knockdown effectively inhibits the progression of rectal cancer by suppressing HMGB1 expression and promoting apoptosis of rectal cancer cells". Molecular Medicine Reports 14, no. 1 (2016): 1026-1032. https://doi.org/10.3892/mmr.2016.5340
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