Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress 2023 EHA Congress 2023 ASCO Annual Meeting
Clinical Collections
Advances in Alzheimer’s

At a glance: The ONWARDS insulin icodec trials

A round-up of the ONWARDS phase 3 clinical trials evaluating the novel weekly insulin icodec in people with diabetes.
ADVANCED SEARCH
Log in
Top
BMC Cancer
Published in: BMC Cancer 1/2018

Open Access 01-12-2018 | Research article

Expression of Reg IV and SOX9 and their correlation in human gastric cancer

Authors: Na Zhang, Dandan Chai, Huifen Du, Kesheng Li, Wenguang Xie, Xingwen Li, Rong Yang, Xiaowen Lian, Yang Xu

Published in: BMC Cancer | Issue 1/2018

Login to get access

Abstract

Background

Reg IV is a member of the regenerating gene family and has been demonstrated to be overexpressed in gastric cancer. However, the functional mechanism of Reg IV in gastric cancer is still unclear.

Methods

Expression of Reg IV and SOX9 were investigated by immunohistochemistry (IHC) and real-time PCR, and the correlation between the expression of Reg IV and SOX9 was analyzed in gastric cancer tissues. Reg IV expression vectors and a siRNA of Reg IV and SOX9 were transfected into human gastric cancer cells and the protein and mRNA levels of Reg IV and SOX9 were investigated by western blot and real-time PCR. The invasion and migration ability of gastric cancer cells with overexpressed Reg IV and with gene silence of Reg IV and SOX9 were examined by transwell chambers and wound healing assay.

Results

The Reg IV and SOX9 protein expression levels were both significantly higher in gastric cancer tissues compared with adjacent tissues (p = 0.022, p = 0.003). Reg IV protein expression significantly correlated with tumor invasion depth (p <  0.001), but had no significant correlations with age, clinical stage or lymph node metastasis. SOX9 protein expression also had no significant correlations with age, clinical stage, tumor invasion depth or lymph node metastasis. Reg IV transcript expression demonstrated a significant correlation with invasion depth and lymph node metastasis (p = 0.005, p <  0.001) and no significant correlations with age, clinical stage, tumor tissue differentiation or tumor size. SOX9 transcript expression demonstrated a significant correlation with invasion depth and tumor tissue differentiation (p = 0.044, p = 0.007) and no significant correlations with age, clinical stage or tumor size. The Reg IV expression showed a positive correlation with the SOX9 expression (p <  0.000, p = 0.008). Overexpression of Reg IV could upregulate SOX9 expression and promote invasiveness and migration of tumor cells, and silencing of Reg IV could downregulate SOX9 and inhibit invasiveness and migration of tumor cells in MKN-45 and AGS cells. On the other hand, silencing of SOX9 could upregulate Reg IV protein expression.

Conclusions

Our study demonstrated that Reg IV positively regulates the expression of SOX9 and is involved in tumor cell invasion and migration in gastric cancer.
Appendix
Available only for authorised users
Literature
1.
Wroblewski LE, Peek RM Jr, Wilson KT. Helicobacter pylori and gastric cancer: factors that modulate disease risk. Clin Microbiol Rev. 2010;23:713–39.CrossRefPubMedPubMedCentral
2.
Steeg PS. Tumor metastasis: mechanistic insights and clinical challenges. Nat Med. 2006;12:895–904.CrossRefPubMed
3.
4.
Coghlin C, Murray GI. Current and emerging concepts in tumour metastasis. J Pathol. 2010;222:1–15.CrossRefPubMed
5.
Gao P, Xing AY, Zhou GY, Zhang TG, Zhang JP, Gao C, et al. The molecular mechanism of microRNA-145 to suppress invasion-metastasis cascade in gastric cancer. Oncogene. 2013;32:491–501.CrossRefPubMed
6.
Hartupee JC, Zhang H, Bonaldo MF, Soares MB, Dieckgraefe BK. Isolation and characterization of a cDNA encoding a novel member of the human regenerating protein family: Reg IV. Biochim Biophys Acta. 2001;1518:287–93.CrossRefPubMed
7.
Miyagawa K, Sakakura C, Kin S, Nakase Y, Fukuda K, Hagiwara A, et al. Over expression of Reg IV in peritoneal dissemination of gastric cancer. Gan To Kagaku Ryoho. 2004;31:1909–11.PubMed
8.
Miyagawa K, Sakakura C, Nakashima S, Yoshikawa T, Fukuda K, Kin S, et al. Overexpression of Reg IV in peritoneal dissemination of gastric cancer and its potential as a novel marker for the detection of peritoneal micrometastasis. Anticancer Res. 2008;28:1169–79.PubMed
9.
Violette S, Festor E, Pandrea-Vasile I, Mitchell V, Adida C, Dussaulx E, et al. Reg IV, a new member of the regenerating gene family, is overexpressed in colorectal carcinomas. Int J Cancer. 2003;103:185–93.CrossRefPubMed
10.
Zhang Y, Lai M, Lv B, Gu X, Wang H, Zhu Y, et al. Overexpression of Reg IV in colorectal adenoma. Cancer Lett. 2003;200:69–76.CrossRefPubMed
11.
He XJ, Jiang XT, Ma YY, Xia YJ, Wang HJ, Guan TP, et al. REG4 contributes to the invasiveness of pancreatic cancer by upregulating MMP-7 and MMP-9. Cancer Sci. 2012;103:2082–91.CrossRefPubMed
12.
Takehara A, Eguchi H, Ohigashi H, Ishikawa O, Kasugai T, Hosokawa M, et al. Novel tumor marker reg4 detected in serum of patients with resectable pancreatic cancer and feasibility for antibody therapy targeting reg4. Cancer Sci. 2006;97:1191–7.CrossRefPubMed
13.
Gu Z, Rubin MA, Yang Y, Deprimo SE, Zhao H, Horvath S, et al. Reg IV: a promising marker of hormone refractory metastatic prostate cancer. Clin Cancer Res. 2005;11:2237–43.CrossRefPubMed
14.
Guo Y, Xu J, Li N, Gao F, Huang P. Reg IV potentiates colorectal carcinoma cell migration and invasion via its CRD domain. Cancer Genet Cytogenet. 2010;199:38–44.CrossRefPubMed
15.
Rafa L, Dessein AF, Devisme L, Buob D, Truant S, Porchet N, et al. REG4 acts as a mitogenic, motility and pro-invasive factor for colon cancer cells. Int J Oncol. 2010;36:689–98.PubMed
16.
Bishnupuri KS, Luo Q, Murmu N, Houchen CW, Anant S, Dieckgraefe BK. Reg IV activates the epidermal growth factor receptor/Akt/AP-1 signaling pathway in Colon adenocarcinomas. Gastroenterology. 2006;130:137–49.CrossRefPubMed
17.
Kuniyasu H, Oue N, Sasahira T, Yi L, Moriwaka Y, Shimomoto T, et al. Reg IV enhances peritoneal metastasis in gastric carcinomas. Cell Prolif. 2009;42:110–21.CrossRefPubMed
18.
Mitani Y, Oue N, Matsumura S, Yoshida K, Noguchi T, Ito M, et al. Reg IV is a serum biomarker for gastric cancer patients and predicts response to 5-fluorouracil-based chemotherapy. Oncogene. 2007;26:4383–93.CrossRefPubMed
19.
Huang J, Yang Y, Yang J, Li X. Regenerating gene family member 4 promotes growth and migration of gastric cancer through protein kinase B pathway. Int J Clin Exp Med. 2014;7:3037–44.PubMedPubMedCentral
20.
Foster JW, Dominguez-Steglich MA, Guioli S, Kwok C, Weller PA, Stevanović M, et al. Campomelic dysplasia and autosomal sex reversal caused by mutations in an SRY-related gene. Nature. 1994;372:525–30.CrossRefPubMed
21.
Wagner T, Wirth J, Meyer J, Zabel B, Held M, Zimmer J, et al. Autosomal sex reversal and campomelic dysplasia are caused by mutations in and around the SRY-related gene SOX9. Cell. 1994;79:1111–20.CrossRefPubMed
22.
Xia S, Feng Z, Qi X, Yin Y, Jin J, Wu Y, et al. Clinical implication of Sox9 and activated Akt expression in pancreatic ductal adenocarcinoma. Med Oncol. 2015;32:358.CrossRefPubMed
23.
Ling S, Chang X, Schultz L, Lee TK, Chaux A, Marchionni L, et al. An EGFR-ERK-SOX9 signaling cascade links urothelial development and regeneration to cancer. Cancer Res. 2011;71:3812–21.CrossRefPubMedPubMedCentral
24.
Yasui W, Oue N, Sentani K, Sakamoto N, Motoshita J. Transcriptome dissection of gastric cancer: identification of novel diagnostic and therapeutic targets from pathology specimens. Pathol Int. 2009;59:121–36.CrossRefPubMed
25.
Sinicrope FA, Ruan SB, Cleary KR, Stephens LC, Lee JJ, Levin B. Bcl-2 and p53 oncoprotein expression during colorectal tumorigenesis. Cancer Res. 1995;55:237–41.PubMed
26.
Link AJ, LaBaer J. Trichloroacetic acid (TCA) precipitation of proteins. Cold Spring Harb Protoc. 2011;2011:993–4.PubMed
27.
Liang CC, Park AY, Guan JL. In vitro scratch assay: a convenient and inexpensive method for analysis of cell migration in vitro. Nat Protoc. 2007;2:329–33.CrossRefPubMed
28.
Wang Z, Xu H, Jiang L, Zhou X, Lu C, Zhang X. Positive association of heparanase expression with tumor invasion and lymphatic metastasis in gastric carcinoma. Mod Pathol. 2005;18:205–11.CrossRefPubMed
29.
Moon JH, Fujiwara Y, Nakamura Y, Okada K, Hanada H, Sakakura C, et al. REG IV as a potential biomarker for peritoneal dissemination in gastric adenocarcinoma. J Surg Oncol. 2012;105:189–94.CrossRefPubMed
30.
Jiang SS, Fang WT, Hou YH, Huang SF, Yen BL, Chang JL, et al. Upregulation of SOX9 in lung adenocarcinoma and its involvement in the regulation of cell growth and tumorigenicity. Clin Cancer Res. 2010;16:4363–73.CrossRefPubMed
31.
Wang X, Ju Y, Zhou MI, Liu X, Zhou C. Upregulation of SOX9 promotes cell proliferation, migration and invasion in lung adenocarcinoma. Oncol Lett. 2015;10:990–4.CrossRefPubMedPubMedCentral
32.
Thomsen MK, Ambroisine L, Wynn S, Cheah KS, Foster CS, Fisher G, et al. SOX9 elevation in the prostate promotes proliferation and cooperates with PTEN loss to drive tumor formation. Cancer Res. 2010;70:979–87.CrossRefPubMedPubMedCentral
33.
Sashikawa Kimura M, Mutoh H, Sugano K. SOX9 is expressed in normal stomach, intestinal metaplasia, and gastric carcinoma in humans. J Gastroenterol. 2011;46:1292–9.CrossRefPubMed
34.
Zhou CJ, Guo JQ, Zhu KX, Zhang QH, Pan CR, Xu WH, et al. Elevated expression of SOX9 is related with the progression of gastric carcinoma. Diagn Cytopathol. 2011;39:105–9.CrossRefPubMed
35.
Sun M, Uozaki H, Hino R, Kunita A, Shinozaki A, Ushiku T, et al. SOX9 expression and its methylation status in gastric cancer. Virchows Arch. 2012;460:271–9.CrossRefPubMed
36.
de Sousa Abreu R, Penalva LO, Marcotte EM, Vogel C. Global signatures of protein and mRNA expression levels. Mol BioSyst. 2009;5:1512–26.PubMed
Metadata
Title
Expression of Reg IV and SOX9 and their correlation in human gastric cancer
Authors
Na Zhang
Dandan Chai
Huifen Du
Kesheng Li
Wenguang Xie
Xingwen Li
Rong Yang
Xiaowen Lian
Yang Xu
Publication date
01-12-2018
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2018
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/s12885-018-4285-x

Other articles of this Issue 1/2018

BMC Cancer 1/2018 Go to the issue

Research article

Adjuvant trastuzumab duration trials in HER2 positive breast cancer – what results would be practice-changing? Persephone investigator questionnaire prior to primary endpoint results

Research article

Analysis of microarrays of miR-34a and its identification of prospective target gene signature in hepatocellular carcinoma

Research article

Prognostic value of serum CYFRA 21-1 1 in patients with anal canal squamous cell carcinoma treated with radio(chemo)therapy

Research article

Discovery of a diagnostic biomarker for colon cancer through proteomic profiling of small extracellular vesicles

Research article

APC gene is modulated by hsa-miR-135b-5p in both diffuse and intestinal gastric cancer subtypes

Research article

Efficacy of a hypnosis-based intervention to improve well-being during cancer: a comparison between prostate and breast cancer patients
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine
Image Credits