Abstract
Prostate cancer is the most commonly diagnosed cancer among men and is the second leading cause of cancer-associated deaths among men in the world. Unfortunately, treatment failures are common due to the metastasis and chemoresistance, but the underlying molecular mechanism remains unclear. Accumulating evidence has indicated that the deregulation of DNA-binding protein High Mobility Group A2 (HMGA2) is associated with the development and progression of cancer. This study aimed to explore the expression of HMGA2 in prostate cancer tissues and its correlation to the clinical pathology of prostate cancer, and to discuss the role of HMGA2 in the development of prostate cancer. The results showed that the expression of HMGA2 messenger RNA (mRNA) in the prostate cancer tissues and cells was significantly higher than that in normal prostate tissues and cells (p < 0.05), and the positive expression rate of HMGA2 mRNA in the prostate cancer tissues from patients with positive lymph node metastasis or with high Gleason grade was significantly higher than that from patients with negative lymph node metastasis or with low Gleason grade (p < 0.05). In order to explore the role of HMGA2 in prostate cancer, the expression of HMGA2 in the human prostate cancer PC3 cell line was downregulated by RNA interference. Then, the changes in proliferation, apoptosis, invasion, and migration of PC3 cells were examined by MTT test, PI staining, Annexin V-FITC staining, and Transwell chamber assay. Results showed that the abilities of proliferation, invasion, and migration were suppressed in HMGA2 knockdown PC3 cells, and the abilities of apoptosis were enhanced in HMGA2 knockdown PC3 cells. The expression of cyclin A and vimentin was downregulated in HMGA2 knockdown PC3 cells, and the expression of caspase 3 and E-cadherin was upregulated in HMGA2 knockdown PC3 cells. Taken together, the overexpression of HMGA2 in prostate cancer might be related to the tumorigenesis, invasion, and metastasis of prostate cancer, the downregulation of HMGA2 could inhibit cellular proliferation, invasion, and metastasis, and improve cellular apoptosis in prostate cancer, which might be a potential target for the treatment of prostate cancer.
Similar content being viewed by others
References
James ND, Spears MR, Clarke NW, Dearnaley DP, De Bono JS, Gale J, et al. Survival with newly diagnosed metastatic prostate cancer in the “docetaxel era”: data from 917 patients in the control arm of the stampede trial (mrc pr08, cruk/06/019). Eur Urol. 2014. doi:10.1016/j.eururo.2014.1009.1032.
Zhang T, Zhang L, Yuan Q, Wang X, Zhang Y, Wang J, et al. The noninvasive detection of rarbeta2 promoter methylation for the diagnosis of prostate cancer. Cell Biochem Biophys. 2015;71:925–30.
Kiljunen T, Kangasmaki A, Aaltonen A, Kairemo K, Partanen K, Joensuu G, et al. Vmat technique enables concomitant radiotherapy of prostate cancer and pelvic bone metastases. Acta Oncol. 2015;54(6):847–53.
Li D, Zhao LN, Zheng XL, Lin P, Lin F, Li Y, et al. Sox2 is involved in paclitaxel resistance of the prostate cancer cell line pc-3 via the pi3k/akt pathway. Mol Med Rep. 2014;10:3169–76.
Patrikidou A, Loriot Y, Eymard JC, Albiges L, Massard C, Ileana E, et al. Who dies from prostate cancer? Prostate Cancer Prostatic Dis. 2014;17:348–52.
Shi X, Tian B, Ma W, Zhang N, Qiao Y, Li X, et al. A novel anti-proliferative role of hmga2 in induction of apoptosis through caspase 2 in primary human fibroblast cells. Biosci Rep. 2015;35(1). doi:10.1042/BSR20140112.
Reeves R. Molecular biology of hmga proteins: hubs of nuclear function. Gene. 2001;277:63–81.
Hammond SM, Sharpless NE. Hmga2, micrornas, and stem cell aging. Cell. 2008;135:1013–6.
Kim TH, Song JY, Park H, Jeong JY, Kwon AY, Heo JH, et al. Mir-145, targeting high-mobility group a2, is a powerful predictor of patient outcome in ovarian carcinoma. Cancer Lett. 2015;356:937–45.
Lee J, Ha S, Jung CK, Lee HH. High-mobility-group a2 overexpression provokes a poor prognosis of gastric cancer through the epithelial-mesenchymal transition. Int J Oncol. 2015. doi:10.3892/ijo.2015.2947.
Dirat B, Ader I, Golzio M, Massa F, Mettouchi A, Laurent K, et al. Inhibition of the gtpase rac1 mediates the antimigratory effects of metformin in prostate cancer cells. Mol Cancer Ther. 2015;14:586–96.
Xia YY, Yin L, Tian H, Guo WJ, Jiang N, Jiang XS, et al. Hmga2 is associated with epithelial-mesenchymal transition and can predict poor prognosis in nasopharyngeal carcinoma. OncoTargets Ther. 2015;8:169–76.
Kaur H, Hutt-Cabezas M, Weingart MF, Xu J, Kuwahara Y, Erdreich-Epstein A, et al. The chromatin-modifying protein hmga2 promotes atypical teratoid/rhabdoid cell tumorigenicity. J Neuropathol Exp Neurol. 2015;74:177–85.
Ding X, Wang Y, Ma X, Guo H, Yan X, Chi Q, et al. Expression of hmga2 in bladder cancer and its association with epithelial-to-mesenchymal transition. Cell Prolif. 2014;47:146–51.
Bai YH, Wang JP, Yang M, Zeng Y, Jiang HY. Sirna-hmga2 weakened ages-induced epithelial-to-mesenchymal transition in tubular epithelial cells. Biochem Biophys Res Commun. 2015;457:730–5.
Thuault S, Tan EJ, Peinado H, Cano A, Heldin CH, Moustakas A. Hmga2 and smads co-regulate snail1 expression during induction of epithelial-to-mesenchymal transition. J Biol Chem. 2008;283:33437–46.
Song HM, Lee JE, Kim JH. Ubiquitin c-terminal hydrolase-l3 regulates emt process and cancer metastasis in prostate cell lines. Biochem Biophys Res Commun. 2014;452:722–7.
Yu KR, Park SB, Jung JW, Seo MS, Hong IS, Kim HS, et al. Hmga2 regulates the in vitro aging and proliferation of human umbilical cord blood-derived stromal cells through the mtor/p70s6k signaling pathway. Stem Cell Res. 2013;10:156–65.
Shlapobersky M, Sanders R, Clark C, Spector DH. Repression of hmga2 gene expression by human cytomegalovirus involves the ie2 86-kilodalton protein and is necessary for efficient viral replication and inhibition of cyclin a transcription. J Virol. 2006;80:9951–61.
Tessari MA, Gostissa M, Altamura S, Sgarra R, Rustighi A, Salvagno C, et al. Transcriptional activation of the cyclin a gene by the architectural transcription factor hmga2. Mol Cell Biol. 2003;23:9104–16.
Acknowledgments
This study was supported by the National Natural Science Foundation of China (No. 81402226).
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Cai, J., Shen, G., Liu, S. et al. Downregulation of HMGA2 inhibits cellular proliferation and invasion, improves cellular apoptosis in prostate cancer. Tumor Biol. 37, 699–707 (2016). https://doi.org/10.1007/s13277-015-3853-9
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s13277-015-3853-9