Expression pattern of the PRDX2, RAB1A, RAB1B, RAB5A and RAB25 genes in normal and cancer cervical tissues

Nikoshkov,Andrej; Broliden,Kristina; Attarha,Sanaz; Sviatoha,Vitali; Hellström,Ann‑Cathrin; Mints,Miriam; Andersson,Sonia

doi:10.3892/ijo.2014.2724

Expression pattern of the PRDX2, RAB1A, RAB1B, RAB5A and RAB25 genes in normal and cancer cervical tissues

Authors:
- Andrej Nikoshkov
- Kristina Broliden
- Sanaz Attarha
- Vitali Sviatoha
- Ann‑Cathrin Hellström
- Miriam Mints
- Sonia Andersson
View Affiliations

Affiliations: Department of Women's and Children's Health, Division of Obstetrics and Gynecology, Karolinska Institute, Karolinska University Hospital Solna, 171 76 Stockholm, Sweden, Department of Medicine Solna, Unit of Infectious Diseases, Center for Molecular Medicine, Karolinska Institute, Karolinska University Hospital, 171 76 Stockholm, Sweden, Department of Oncology‑Pathology, Karolinska Institute, 171 76 Stockholm, Sweden, Department of Gynecological Oncology, Radiumhemmet, Karolinska University Hospital, 171 76 Stockholm, Sweden
Published online on: October 23, 2014 https://doi.org/10.3892/ijo.2014.2724
Pages: 107-112

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

Cervical cancer is the second most prevalent malignancy among women worldwide, and additional objective diagnostic markers for this disease are needed. Given the link between cancer development and alternative splicing, we aimed to analyze the splicing patterns of the PRDX2, RAB1A, RAB1B, RAB5A and RAB25 genes, which are associated with different cancers, in normal cervical tissue, preinvasive cervical lesions and invasive cervical tumors, to identify new objective diagnostic markers. Biopsies of normal cervical tissue, preinvasive cervical lesions and invasive cervical tumors, were subjected to rapid amplification of cDNA 3' ends (3' RACE) RT‑PCR. Resulting PCR products were analyzed on agarose gels, gel‑purified and sequenced. Normal cervical tissue, preinvasive cervical lesions and invasive cervical tumors contained one PCR product corresponding to full‑length PRDX2, RAB5A and RAB25 transcripts. All tissues contained two RAB1A‑specific PCR products corresponding to the full‑length transcript and one new alternatively spliced RAB1A transcript. Invasive cervical tumors contained one PCR product corresponding to the full‑length RAB1B transcript, while all normal cervical tissue and preinvasive cervical lesions contained both the full‑length RAB1B transcript and three new alternatively spliced RAB1B transcripts. Alternative splicing of the RAB1A transcript occurs in all cervical tissues, while alternative splicing of the RAB1B transcript occurs in normal cervical tissue and in preinvasive cervical lesions; not in invasive cervical tumors.

View Figures

View References

1	Black DL: Mechanisms of alternative pre-messenger RNA splicing. Annu Rev Biochem. 72:291–336. 2003. View Article : Google Scholar : PubMed/NCBI
2	Singh RK and Cooper TA: Pre-mRNA splicing in disease and therapeutics. Trends Mol Med. 18:472–482. 2012. View Article : Google Scholar : PubMed/NCBI
3	Pal S, Gupta R and Davuluri RV: Alternative transcription and alternative splicing in cancer. Pharmacol Ther. 136:283–294. 2012. View Article : Google Scholar
4	Garcia-Blanco MA, Baraniak AP and Lasda EL: Alternative splicing in disease and therapy. Nat Biotechnol. 22:535–546. 2004. View Article : Google Scholar : PubMed/NCBI
5	Mills AA: p53: link to the past, bridge to the future. Genes Dev. 19:2091–2099. 2005. View Article : Google Scholar : PubMed/NCBI
6	Lamolle G, Marin M and Alvarez-Valin F: Silent mutations in the gene encoding the p53 protein are preferentially located in conserved amino acid positions and splicing enhancers. Mutat Res. 600:102–112. 2006. View Article : Google Scholar : PubMed/NCBI
7	Neklason DW, Solomon CH, Dalton AL, Kuwada SK and Burt RW: Intron 4 mutation in APC gene results in splice defect and attenuated FAP phenotype. Fam Cancer. 3:35–40. 2004. View Article : Google Scholar : PubMed/NCBI
8	Mazoyer S, Puget N, Perrin-Vidoz L, Lynch HT, Serova-Sinilnikova OM and Lenoir GM: A BRCA1 nonsense mutation causes exon skipping. Am J Hum Genet. 62:713–715. 1998. View Article : Google Scholar : PubMed/NCBI
9	Ghigna C, Valacca C and Biamonti G: Alternative splicing and tumor progression. Curr Genomics. 9:556–570. 2008. View Article : Google Scholar : PubMed/NCBI
10	David CJ and Manley JL: Alternative pre-mRNA splicing regulation in cancer: pathways and programs unhinged. Genes Dev. 24:2343–2364. 2010. View Article : Google Scholar : PubMed/NCBI
11	Bosch FX and Muñoz N: The viral etiology of cervical cancer. Virus Res. 89:183–190. 2002. View Article : Google Scholar : PubMed/NCBI
12	Walboomers JM, Jacobs MV, Manos MM, et al: Human papillomavirus is a necessary cause of invasive cervical cancer worldwide. J Pathol. 189:12–19. 1999. View Article : Google Scholar : PubMed/NCBI
13	zur Hausen H: Papillomaviruses and cancer: from basic studies to clinical application. Nat Rev Cancer. 2:342–350. 2002.PubMed/NCBI
14	Muñoz N, Bosch FX, de Sanjosé S, et al: Epidemiologic classification of human papillomavirus types associated with cervical cancer. N Engl J Med. 348:518–527. 2003.
15	Muñoz N: Human papillomavirus and cancer: the epidemiological evidence. J Clin Virol. 19:1–5. 2000.
16	Clifford GM, Smith JS, Plummer M, Muñoz N and Franceschi S: Human papillomavirus types in invasive cervical cancer worldwide: a meta-analysis. Br J Cancer. 88:63–73. 2003. View Article : Google Scholar : PubMed/NCBI
17	Sundström K, Ploner A, Dahlström LA, et al: Prospective study of HPV16 viral load and risk of in situ and invasive squamous cervical cancer. Cancer Epidemiol Biomarkers Prev. 22:150–158. 2013.PubMed/NCBI
18	Lazo PA: Papillomavirus integration: prognostic marker in cervical cancer? Am J Obstet Gynecol. 176:1121–1122. 1997. View Article : Google Scholar : PubMed/NCBI
19	Kalantari M, Karlsen F, Kristensen G, Holm R, Hagmar B and Johansson B: Disruption of the E1 and E2 reading frames of HPV 16 in cervical carcinoma is associated with poor prognosis. Int J Gynecol Pathol. 17:146–153. 1998. View Article : Google Scholar : PubMed/NCBI
20	Kalantari M, Blennow E, Hagmar B and Johansson B: Physical state of HPV16 and chromosomal mapping of the integrated form in cervical carcinomas. Diagn Mol Pathol. 10:46–54. 2001. View Article : Google Scholar : PubMed/NCBI
21	Romanczuk H and Howley PM: Disruption of either the E1 or the E2 regulatory gene of human papillomavirus type 16 increases viral immortalization capacity. Proc Natl Acad Sci USA. 89:3159–3163. 1992. View Article : Google Scholar : PubMed/NCBI
22	McPhillips MG, Veerapraditsin T, Cumming SA, et al: SF2/ASF binds the human papillomavirus type 16 late RNA control element and is regulated during differentiation of virus-infected epithelial cells. J Virol. 78:10598–10605. 2004. View Article : Google Scholar
23	Cheunim T, Zhang J, Milligan SG, McPhillips MG and Graham SV: The alternative splicing factor hnRNP A1 is up-regulated during virus-infected epithelial cell differentiation and binds the human papillomavirus type 16 late regulatory element. Virus Res. 131:189–198. 2008. View Article : Google Scholar
24	Hellman K, Alaiya AA, Becker S, et al: Differential tissue-specific protein markers of vaginal carcinoma. Br J Cancer. 100:1303–1314. 2009. View Article : Google Scholar : PubMed/NCBI
25	Shimada K, Uzawa K, Kato M, et al: Aberrant expression of RAB1A in human tongue cancer. Br J Cancer. 92:1915–1921. 2005. View Article : Google Scholar : PubMed/NCBI
26	Sun T, Wang X, He HH, et al: MiR-221 promotes the development of androgen independence in prostate cancer cells via downregulation of HECTD2 and RAB1A. Oncogene. 33:2790–2800. 2014. View Article : Google Scholar : PubMed/NCBI
27	Liu SS, Chen XM, Zheng HX, Shi SL and Li Y: Knockdown of Rab5a expression decreases cancer cell motility and invasion through integrin-mediated signaling pathway. J Biomed Sci. 18:582011. View Article : Google Scholar : PubMed/NCBI
28	Cheng KW, Lahad JP, Kuo WL, et al: The RAB25 small GTPase determines aggressiveness of ovarian and breast cancers. Nat Med. 10:1251–1256. 2004. View Article : Google Scholar : PubMed/NCBI
29	Hutagalung AH and Novick PJ: Role of Rab GTPases in membrane traffic and cell physiology. Physiol Rev. 91:119–149. 2011. View Article : Google Scholar : PubMed/NCBI
30	Hernández-Alcoceba R, del Peso L and Lacal JC: The Ras family of GTPases in cancer cell invasion. Cell Mol Life Sci. 57:65–76. 2000.PubMed/NCBI
31	Münger K, Baldwin A, Edwards KM, et al: Mechanisms of human papillomavirus-induced oncogenesis. J Virol. 78:11451–11460. 2004.