Increased SPC24 in prostatic diseases and diagnostic value of SPC24 and its interacting partners in prostate cancer

Chen,Suixia; Wang,Xiao; Zheng,Shengfeng; Li,Hongwen; Qin,Shouxu; Liu,Jiayi; Jia,Wenxian; Shao,Mengnan; Tan,Yanjun; Liang,Hui; Song,Weiru; Lu,Shaoming; Liu,Chengwu; Yang,Xiaoli

doi:10.3892/etm.2021.10355

Increased SPC24 in prostatic diseases and diagnostic value of SPC24 and its interacting partners in prostate cancer

Authors:
- Suixia Chen
- Xiao Wang
- Shengfeng Zheng
- Hongwen Li
- Shouxu Qin
- Jiayi Liu
- Wenxian Jia
- Mengnan Shao
- Yanjun Tan
- Hui Liang
- Weiru Song
- Shaoming Lu
- Chengwu Liu
- Xiaoli Yang
View Affiliations

Affiliations: Scientific Research Center, Guilin Medical University, Guilin, Guangxi 541100, P.R. China, Department of Anatomy, Faculty of Basic Medical Sciences, Guilin Medical University, Guilin, Guangxi 541100, P.R. China, Department of Andrology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi 530021, P.R. China, Center for Reproductive Medicine, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong 250200, P.R. China, Department of Pathophysiology, Guangxi Medical University, Nanning, Guangxi 530021, P.R. China
Published online on: June 30, 2021 https://doi.org/10.3892/etm.2021.10355
Article Number: 923
Copyright: © Chen 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

SPC24 is a crucial component of the mitotic checkpoint machinery in tumorigenesis. High levels of SPC24 have been found in various cancers, including breast cancer, lung cancer, liver cancer, osteosarcoma and thyroid cancer. However, to the best of our knowledge, the impact of SPC24 on prostate cancer (PCa) and other prostate diseases remains unclear. In the present study expression of global SPC24 messenger RNA (mRNA) was assessed in a subset of patients with PCa included in The Cancer Genome Atlas (TCGA) database. Increased levels of SPC24 expression were found in PCa patients >60 years old compared to patients <60 and increased SPC24 expression was also associated with higher levels of prostate specific antigen (P<0.05) and lymph node metastasis (P<0.05). Higher levels of SPC24 expression were associated with negative outcomes in PCa patients (P<0.05). Furthermore, in Chinese patients with prostatitis, benign prostatic hypertrophy (BPH) and PCa, SPC24 was expressed at significantly higher levels than that in adjacent/normal tissues, as assessed by reverse transcription‑quantitative polymerase chain reaction, immunohistochemistry and western blotting. High expression of SPC24 was associated with high Gleason stages (IV and V; P<0.05). Further analysis, based on Gene Ontology and pathway functional enrichment analysis, suggested that nuclear division cycle 80 (NDC80), an SPC24 protein interaction partner, and mitotic spindle checkpoint serine/threonine‑protein kinase BUB1 (BUB1), a core subunit of the spindle assembly checkpoint, may be associated with SPC24 in PCa development. Finally, using binary logistic regression, algorithms combining the receiver operating characteristic between SPC24 and BUB1 or NDC80 indicated that a combination of these markers may provide better PCa diagnosis ability than other PCa diagnosis markers. Taken together, these findings suggest that SPC24 may be a promising prostate disease biomarker.

View Figures

View References

1	DeLuca JG and Musacchio A: Structural organization of the kinetochore-microtubule interface. Curr Opin Cell Biol. 24:48–56. 2012.PubMed/NCBI View Article : Google Scholar
2	Cheeseman IM and Desai A: Molecular architecture of the kinetochore-microtubule interface. Nat Rev Mol Cell Biol. 9:33–46. 2008.PubMed/NCBI View Article : Google Scholar
3	Wilson-Kubalek EM, Cheeseman IM, Yoshioka C, Desai A and Milligan RA: Orientation and structure of the Ndc80 complex on the microtubule lattice. J Cell Biol. 182:1055–1061. 2008.PubMed/NCBI View Article : Google Scholar
4	Dominguez-Brauer C, Thu KL, Mason JM, Blaser H, Bray MR and Mak TW: Targeting mitosis in cancer: Emerging strategies. Mol Cell. 60:524–536. 2015.PubMed/NCBI View Article : Google Scholar
5	Ma L, McQueen J, Cuschieri L, Vogel J and Measday V: Spc24 and Stu2 promote spindle integrity when DNA replication is stalled. Mol Biol Cell. 18:2805–2816. 2007.PubMed/NCBI View Article : Google Scholar
6	Bharadwaj R and Yu H: The spindle checkpoint, aneuploidy, and cancer. Oncogene. 23:2016–2027. 2004.PubMed/NCBI View Article : Google Scholar
7	Siegel RL, Miller KD and Jemal A: Cancer statistics, 2018. CA Cancer J Clin. 68:7–30. 2018.PubMed/NCBI View Article : Google Scholar
8	Nelson WG, De Marzo AM and Isaacs WB: Prostate cancer. N Engl J Med. 349:366–381. 2003.PubMed/NCBI View Article : Google Scholar
9	Gutiérrez-González E, Castelló A, Fernández-Navarro P, Castaño-Vinyals G, Llorca J, Salas D, Salcedo-Bellido I, Aragonés N, Fernández-Tardón G, Alguacil J, et al: Dietary zinc and risk of prostate cancer in Spain: MCC-Spain Study. Nutrients. 11(18)2018.PubMed/NCBI View Article : Google Scholar
10	Hung SC, Lai SW, Tsai PY, Chen PC, Wu HC, Lin WH and Sung FC: Synergistic interaction of benign prostatic hyperplasia and prostatitis on prostate cancer risk. Br J Cancer. 108:1778–1783. 2013.PubMed/NCBI View Article : Google Scholar
11	Dai X, Fang X, Ma Y and Xianyu J: Benign prostatic hyperplasia and the risk of prostate cancer and bladder cancer: A meta-analysis of observational studies. Medicine (Baltimore). 95(e3493)2016.PubMed/NCBI View Article : Google Scholar
12	Boorjian SA, Eastham JA, Graefen M, Guillonneau B, Karnes RJ, Moul JW, Schaeffer EM, Stief C and Zorn KC: A critical analysis of the long-term impact of radical prostatectomy on cancer control and function outcomes. Eur Urol. 61:664–675. 2012.PubMed/NCBI View Article : Google Scholar
13	Sharma N and Baruah MM: The microRNA signatures: Aberrantly expressed miRNAs in prostate cancer. Clin Transl Oncol. 21:126–144. 2019.PubMed/NCBI View Article : Google Scholar
14	Zhou J, Pei Y, Chen G, Cao C, Liu J, Ding C, Wang D, Sun L, Xu P and Niu G: SPC24 Regulates breast cancer progression by PI3K/AKT signaling. Gene. 675:272–277. 2018.PubMed/NCBI View Article : Google Scholar
15	Zhou J, Yu Y, Pei Y, Cao C, Ding C, Wang D, Sun L and Niu G: A potential prognostic biomarker SPC24 promotes tumorigenesis and metastasis in lung cancer. Oncotarget. 8:65469–65480. 2017.PubMed/NCBI View Article : Google Scholar
16	Yin H, Meng T, Zhou L, Chen H and Song D: SPC24 is critical for anaplastic thyroid cancer progression. Oncotarget. 8:21884–21891. 2017.PubMed/NCBI View Article : Google Scholar
17	Sheng J, Yin M, Sun Z, Kang X, Liu D, Jiang K, Xu J, Zhao F, Guo Q and Zheng W: SPC24 promotes osteosarcoma progression by increasing EGFR/MAPK signaling. Oncotarget. 8:105276–105283. 2017.PubMed/NCBI View Article : Google Scholar
18	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.PubMed/NCBI View Article : Google Scholar
19	Tokuzumi A, Fukushima S, Miyashita A, Nakahara S, Kubo Y, Yamashita J, Harada M, Nakamura K, Kajihara I, Jinnin M and Ihn H: Cell division cycle-associated protein 1 as a new melanoma-associated antigen. J Dermatol. 43:1399–1405. 2016.PubMed/NCBI View Article : Google Scholar
20	Obara W, Sato F, Takeda K, Kato R, Kato Y, Kanehira M, Takata R, Mimata H, Sugai T, Nakamura Y and Fujioka T: Phase I clinical trial of cell division associated 1 (CDCA1) peptide vaccination for castration resistant prostate cancer. Cancer Sci. 108:1452–1457. 2017.PubMed/NCBI View Article : Google Scholar
21	McCleland ML, Kallio MJ, Barrett-Wilt GA, Kestner CA, Shabanowitz J, Hunt DF, Gorbsky GJ and Stukenberg PT: The vertebrate Ndc80 complex contains Spc24 and Spc25 homologs, which are required to establish and maintain kinetochore-microtubule attachment. Curr Biol. 14:131–137. 2004.PubMed/NCBI View Article : Google Scholar
22	Cui F, Hu J, Fan Y, Tan J and Tang H: Knockdown of spindle pole body component 25 homolog inhibits cell proliferation and cycle progression in prostate cancer. Oncol Lett. 15:5712–5720. 2018.PubMed/NCBI View Article : Google Scholar
23	Hanahan D and Weinberg RA: The hallmarks of cancer: The next generation. Cell. 144:646–674. 2011.PubMed/NCBI View Article : Google Scholar
24	Wei RR, Sorger PK and Harrison SC: Molecular organization of the Ndc80 complex, an essential kinetochore component. Proc Natl Acad Sci USA. 102:5363–5367. 2005.PubMed/NCBI View Article : Google Scholar
25	Wei RR, Schnell JR, Larsen NA, Sorger PK, Chou JJ and Harrison SC: Structure of a central component of the yeast kinetochore: The Spc24p/Spc25p globular domain. Structure. 14:1003–1009. 2006.PubMed/NCBI View Article : Google Scholar
26	Sun SC, Lee SE and Xu YN: Perturbation of SPC25 expression affects meiotic spindle organization, chromosome alignment and spindle assembly checkpoint in mouse oocytes. Cell cycle. 9:4552–4559. 2010.PubMed/NCBI View Article : Google Scholar
27	Zhang T, Zhou Y, Wang HH, Meng TG, Guo L, Ma XS, Shen W, Schatten H and Sun QY: SPC24 is required for meiotic kinetochore-microtubule attachment and production of euploid eggs. Oncotarget. 7:71987–71997. 2016.PubMed/NCBI View Article : Google Scholar
28	Charters GA, Stones CJ, Shelling AN, Baguley BC and Finlay GJ: Centrosomal dysregulation in human metastatic melanoma cell lines. Cancer Genet. 204:477–485. 2011.PubMed/NCBI View Article : Google Scholar
29	Tomonaga T, Matsushita K, Ishibashi M, Nezu M, Shimada H, Ochiai T, Yoda K and Nomura F: Centromere protein H is up-regulated in primary human colorectal cancer and its overexpression induces aneuploidy. Cancer Res. 65:4683–4689. 2005.PubMed/NCBI View Article : Google Scholar
30	Wang H, Gao X, Lu X, Wang Y, Ma C, Shi Z, Zhu F, He B, Xu C and Sun Y: The mitotic regulator Hec1 is a critical modulator of prostate cancer through the long non-coding RNA BX647187 in vitro. Biosci Rep. 35(e00273)2015.PubMed/NCBI View Article : Google Scholar
31	Huang LY, Chang CC, Lee YS, Chang JM, Huang JJ, Chuang SH, Kao KJ, Lau GM, Tsai PY, Liu CW, et al: Activity of a novel Hec1-targeted anticancer compound against breast cancer cell lines in vitro and in vivo. Mol Cancer Ther. 13:1419–1430. 2014.PubMed/NCBI View Article : Google Scholar
32	Chmielewska AE, Tang NH and Toda T: The hairpin region of Ndc80 is important for the kinetochore recruitment of Mph1/MPS1 in fission yeast. Cell Cycle. 15:740–747. 2016.PubMed/NCBI View Article : Google Scholar
33	Tang NH and Toda T: MAPping the Ndc80 loop in cancer: A possible link between Ndc80/Hec1 overproduction and cancer formation. Bioessays. 37:248–256. 2015.PubMed/NCBI View Article : Google Scholar
34	Musacchio A: The molecular biology of spindle assembly checkpoint signaling dynamics. Curr Biol. 25:R1002–R1018. 2015.PubMed/NCBI View Article : Google Scholar
35	Lara-Gonzalez P, Westhorpe FG and Taylor SS: The spindle assembly checkpoint. Curr Biol. 22:R966–R980. 2012.PubMed/NCBI View Article : Google Scholar
36	Ricke RM, Jeganathan KB and van Deursen JM: Bub1 overexpression induces aneuploidy and tumor formation through Aurora B kinase hyperactivation. J Cell Biol. 193:1049–1064. 2011.PubMed/NCBI View Article : Google Scholar
37	Marks LS, Fradet Y, Deras IL, Blasé A, Mathis J, Aubin SM, Cancio AT, Desaulniers M, Ellis WJ, Rittenhouse H and Groskopf J: Pca3 molecular urine assay for prostate cancer in men undergoing repeat biopsy. Urology. 69:532–535. 2007.PubMed/NCBI View Article : Google Scholar
38	Merola R, Tomao L, Antenucci A, Sperduti I, Sentinelli S, Masi S, Mandoj C, Orlandi G, Papalia R, Guaglianone S, et al: Pca3 in prostate cancer and tumor aggressiveness detection on 407 high-risk patients: A national cancer institute experience. J Exp Clin Cancer Res. 34(15)2015.PubMed/NCBI View Article : Google Scholar
39	Mao Z, Ji A, Yang K, He W, Hu Y, Zhang Q, Zhang D and Xie L: Diagnostic performance of PCA3 and hK2 in combination with serum PSA for prostate cancer. Medicine (Baltimore). 97(e12806)2018.PubMed/NCBI View Article : Google Scholar