Coronin 3 negatively regulates G6PC3 in HepG2 cells, as identified by label‑free mass‑spectrometry

Gao,Yunzhen; Li,Ling; Xing,Xiaohua; Lin,Minjie; Zeng,Yongyi; Liu,Xiaolong; Liu,Jingfeng

doi:10.3892/mmr.2017.7002

Coronin 3 negatively regulates G6PC3 in HepG2 cells, as identified by label‑free mass‑spectrometry

Authors:
- Yunzhen Gao
- Ling Li
- Xiaohua Xing
- Minjie Lin
- Yongyi Zeng
- Xiaolong Liu
- Jingfeng Liu
View Affiliations

Affiliations: The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, Fujian 350005, P.R. China, Liver Disease Center, The First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian 350005, P.R. China
Published online on: July 15, 2017 https://doi.org/10.3892/mmr.2017.7002
Pages: 3407-3414

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

Human coronin 3 is involved in many types of cancers, but the underlying molecular mechanisms require further elucidation. The present study demonstrated that coronin 3 is significantly upregulated in clinical primary hepatocellular carcinoma (HCC) samples by reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR) and immunohistochemical staining. Subsequently, proteins that were regulated by coronin 3 in both coronin 3 overexpressing or knocked down HepG2 cells were analyzed by label free mass spectrometry; overall, 249 proteins were identified to be closely regulated by coronin 3, and those coronin 3 regulated proteins were enriched in cellular, physiological and metabolism processes. By further in‑depth pathway analysis, it was demonstrated that those proteins were involved into 94 different pathways. Finally, the expression levels of glucose‑6‑phosphatase catalytic subunit 3 (G6PC3) were confirmed to be negatively regulated by coronin 3, as determined by RT‑qPCR and western blotting. In conclusion, these results indicated that coronin3 is significantly dysregulated in HCC tumor tissues, and may exert its function via regulating G6PC3 expression. These results provide valuable information for further study of coronin 3‑mediated signaling pathways, and implicate coronin 3 as a potential therapeutic target for HCC.

View Figures

View References

1	Iizaka M, Han HJ, Akashi H, Furukawa Y, Nakajima Y, Sugano S, Ogawa M and Nakamura Y: Isolation and chromosomal assignment of a novel human gene, CORO1C, homologous to coronin-like actin-binding proteins. Cytogenet Cell Genet. 88:221–224. 2000. View Article : Google Scholar : PubMed/NCBI
2	McArdle B and Hofmann A: Coronin structure and implications. Subcell Biochem. 48:56–71. 2008. View Article : Google Scholar : PubMed/NCBI
3	Wick M, Bürger C, Brüsselbach S, Lucibello FC and Müller R: Identification of serum-inducible genes: Different patterns of gene regulation during G0->S and G1->S progression. J Cell Sci. 107:227–239. 1994.PubMed/NCBI
4	Chang HY, Sneddon JB, Alizadeh AA, Sood R, West RB, Montgomery K, Chi JT, van de Rijn M, Botstein D and Brown PO: Gene expression signature of fibroblast serum response predicts human cancer progression: Similarities between tumors and wounds. PLoS Biol. 2:E72004. View Article : Google Scholar : PubMed/NCBI
5	Carlier MF and Pantaloni D: Control of actin assembly dynamics in cell motility. J Biol Chem. 282:23005–23009. 2007. View Article : Google Scholar : PubMed/NCBI
6	Samarin SN, Koch S, Ivanov AI, Parkos CA and Nusrat A: Coronin 1C negatively regulates cell-matrix adhesion and motility of intestinal epithelial cells. Biochem Biophys Res Commun. 391:394–400. 2010. View Article : Google Scholar : PubMed/NCBI
7	Thal D, Xavier CP, Rosentreter A, Linder S, Friedrichs B, Waha A, Pietsch T, Stumpf M, Noegel A and Clemen C: Expression of coronin-3 (coronin-1C) in diffuse gliomas is related to malignancy. J Pathol. 214:415–424. 2008. View Article : Google Scholar : PubMed/NCBI
8	Mataki H, Enokida H, Chiyomaru T, Mizuno K, Matsushita R, Goto Y, Nishikawa R, Higashimoto I, Samukawa T, Nakagawa M, et al: Downregulation of the microRNA-1/133a cluster enhances cancer cell migration and invasion in lung-squamous cell carcinoma via regulation of Coronin1C. J Hum Genet. 60:53–61. 2015. View Article : Google Scholar : PubMed/NCBI
9	Ren G, Tian Q, An Y, Feng B, Lu Y, Liang J, Li K, Shang Y, Nie Y, Wang X and Fan D: Coronin 3 promotes gastric cancer metastasis via the up-regulation of MMP-9 and cathepsin K. Mol Cancer. 11:672012. View Article : Google Scholar : PubMed/NCBI
10	Wang ZG, Jia MK, Cao H, Bian P and Fang XD: Knockdown of Coronin-1C disrupts Rac1 activation and impairs tumorigenic potential in hepatocellular carcinoma cells. Oncol Rep. 29:1066–1072. 2013.PubMed/NCBI
11	Wu L, Peng CW, Hou JX, Zhang YH, Chen C, Chen LD and Li Y: Coronin-1C is a novel biomarker for hepatocellular carcinoma invasive progression identified by proteomics analysis and clinical validation. J Exp Clin Cancer Res. 29:172010. View Article : Google Scholar : PubMed/NCBI
12	Tilley FC, Williamson RC, Race PR, Rendall TC and Bass MD: Integration of the Rac1- and actin-binding properties of Coronin-1C. Small GTPases. 6:36–42. 2015. View Article : Google Scholar : PubMed/NCBI
13	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. 25:403–408. 2001. View Article : Google Scholar
14	Gilar M, Olivova P, Daly AE and Gebler JC: Two-dimensional separation of peptides using RP-RP-HPLC system with different pH in first and second separation dimensions. J Sep Sci. 28:1694–1703. 2005. View Article : Google Scholar : PubMed/NCBI
15	Guan DX, Shi J, Zhang Y, Zhao JS, Long LY, Chen TW, Zhang EB, Feng YY, Bao WD, Deng YZ, et al: Sorafenib enriches epithelial cell adhesion molecule-positive tumor initiating cells and exacerbates a subtype of hepatocellular carcinoma through TSC2-AKT cascade. Hepatology. 62:1791–1803. 2015. View Article : Google Scholar : PubMed/NCBI
16	Auld DS and Bergman T: Medium- and short-chain dehydrogenase/reductase gene and protein families: The role of zinc for alcohol dehydrogenase structure and function. Cell Mol Life Sci. 65:3961–3970. 2008. View Article : Google Scholar : PubMed/NCBI
17	Wang W, Xie Q, Zhou X, Yao J, Zhu X, Huang P, Zhang L, Wei J, Xie H, Zhou L and Zheng S: Mitofusin-2 triggers mitochondria Ca²⁺ influx from the endoplasmic reticulum to induce apoptosis in hepatocellular carcinoma cells. Cancer Lett. 358:47–58. 2015. View Article : Google Scholar : PubMed/NCBI
18	Fu W, Sun J, Huang G, Liu JC, Kaufman A, Ryan RJ, Ramanathan SY, Venkatesh T and Singh B: Squamous cell carcinoma-related oncogene (SCCRO) family members regulate cell growth and proliferation through their cooperative and antagonistic effects on cullin neddylation. J Biol Chem. 291:6200–6217. 2016. View Article : Google Scholar : PubMed/NCBI
19	Wang B, Hsu SH, Frankel W, Ghoshal K and Jacob ST: Stat3-mediated activation of microRNA-23a suppresses gluconeogenesis in hepatocellular carcinoma by down-regulating glucose-6-phosphatase and peroxisome proliferator-activated receptor gamma, coactivator 1 alpha. Hepatology. 56:186–197. 2012. View Article : Google Scholar : PubMed/NCBI
20	Zhou C, Licciulli S, Avila JL, Cho M, Troutman S, Jiang P, Kossenkov AV, Showe LC, Liu Q, Vachani A, et al: The Rac1 splice form Rac1b promotes K-ras-induced lung tumorigenesis. Oncogene. 32:903–909. 2013. View Article : Google Scholar : PubMed/NCBI
21	Wu CY, Carpenter ES, Takeuchi KK, Halbrook CJ, Peverley LV, Bien H, Hall JC, DelGiorno KE, Pal D, Song Y, et al: PI3K Regulation of RAC1 Is required for KRAS-induced pancreatic tumorigenesis in mice. Gastroenterology. 147:1405–1416.e7. 2014. View Article : Google Scholar : PubMed/NCBI
22	Yamamoto N, Otsuka T, Kondo A, Matsushima-Nishiwaki R, Kuroyanagi G, Kozawa O and Tokuda H: Rac limits TGF-β-induced VEGF synthesis in osteoblasts. Mol Cell Endocrinol. 405:35–41. 2015. View Article : Google Scholar : PubMed/NCBI
23	Yu JR, Tai Y, Jin Y, Hammell MC, Wilkinson JE, Roe JS, Vakoc CR and Van Aelst L: TGF-β/Smad signaling through DOCK4 facilitates lung adenocarcinoma metastasis. Genes Dev. 29:250–261. 2015. View Article : Google Scholar : PubMed/NCBI
24	Rybakin V and Clemen CS: Coronin proteins as multifunctional regulators of the cytoskeleton and membrane trafficking. Bioessays. 27:625–632. 2005. View Article : Google Scholar : PubMed/NCBI
25	Uetrecht AC and Bear JE: Coronins: The return of the crown. Trends Cell Biol. 16:421–426. 2006. View Article : Google Scholar : PubMed/NCBI
26	Lee AS: Glucose-regulated proteins in cancer: Molecular mechanisms and therapeutic potential. Cancer. 14:263–276. 2014.PubMed/NCBI
27	Li B, Qiu B, Lee DS, Walton ZE, Ochocki JD, Mathew LK, Mancuso A, Gade TP, Keith B, Nissim I and Simonn MC: Fructose-1,6-bisphosphatase opposes renal carcinoma progression. Nature. 513:251–255. 2014. View Article : Google Scholar : PubMed/NCBI
28	Michals K, Pringle K, Pang EJ and Matalon R: Glucose-6-phosphatase as a marker for tumors of liver and kidney origin. Biochem Med. 30:127–130. 1983. View Article : Google Scholar : PubMed/NCBI
29	Guo T, Chen T, Gu C, Li B and Xu C: Genetic and molecular analyses reveal G6PC as a key element connecting glucose metabolism and cell cycle control in ovarian cancer. Tumour Biol. 36:7649–7658. 2015. View Article : Google Scholar : PubMed/NCBI
30	Abbadi S, Rodarte JJ, Abutaleb A, Lavell E, Smith CL, Ruff W, Schiller J, Olivi A, Levchenko A, Guerrero-Cazares H and Quinones-Hinojosa A: Glucose-6-phosphatase is a key metabolic regulator of glioblastoma invasion. Mol Cancer Res. 12:1547–1559. 2014. View Article : Google Scholar : PubMed/NCBI
31	Moissoglu K, Slepchenko BM, Meller N, Horwitz AF and Schwartz MA: In vivo dynamics of Rac-membrane interactions. Mol Biol Cell. 17:2770–2779. 2006. View Article : Google Scholar : PubMed/NCBI
32	Simon AR, Vikis HG, Stewart S, Fanburg BL, Cochran BH and Guan KL: Regulation of STAT3 by direct binding to the Rac1 GTPase. Science. 290:144–147. 2000. View Article : Google Scholar : PubMed/NCBI
33	Sawada N, Li Y and Liao JK: Novel aspects of the roles of Rac1 GTPase in the cardiovascular system. Curr Opin Pharmacol. 10:116–121. 2010. View Article : Google Scholar : PubMed/NCBI