Issue
Expression of MACC1 protein in gastric cancer and its effect on proliferation and invasion of gastric cancer cells
Corresponding Author(s) : Xiannian Zheng
Cellular and Molecular Biology,
Vol. 66 No. 2: Issue 2
Abstract
To detect the expression of metastasis-associated colon cancer gene 1 (MACC1) protein in gastric cancer tissues, and analyze its relationship with clinicopathological parameters of gastric cancer and its effect on proliferation and invasion of gastric cancer cells. Methods: 71 patients with gastric cancer in Fifth Hospital in Wuhan from June 2014 to March 2018 were selected as research subjects. Western blot was used to detect the expression of MACC1 in gastric cancer tissue and normal gastric mucosa tissue, and gastric cancer cell SGC7901 was transfected. Transfection group (transfected with MACC1-siRNA), negative control group (transfected with siRNA-NC) and blank control group (untreated cells) were set up. After transfection, the expressions of MACC1 protein and mRNA in the 3 groups were detected by Western blot and qRT-PCR methods, the cell proliferation was detected by MTT method, and the invasion ability of cells in vitro was detected by Transwell chamber. Results: The expression of MACC1 protein in gastric cancer tissue was higher than the control group (P< 0.05). The expression of MACC1 protein in gastric cancer was related to the differentiation degree, infiltration depth, lymph node metastasis and different stages of gastric cancer (P< 0.05). After transfection, the expressions of MACC1 protein and mRNA in the transfection group was significantly lower than the negative control group and blank group (P< 0.05). There was no significant difference in cell viability between the blank group and negative control group at each time point (P> 0.05). Conclusion: MACC1 was highly expressed in gastric cancer tissues. The expression of MACC1 was related to the differentiation degree, infiltration depth, lymph node metastasis and staging of gastric cancer. Down-regulation of MACC1 could inhibit the proliferation and invasion of gastric cancer cells. This study provided a certain biological basis for early clinical prediction, diagnosis and treatment of gastric cancer.
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- Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of inci¬dence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 2018; 68(6): 394-424.
- Chen W, Zheng R, Baade PD, Zhang S, Zeng H, Bray F, Jemal A, Yu HQ, He, J. Cancer statistics in China, 2015. CA Cancer J Clin 2016; 66(2): 115-132.
- Dong R, Zhang Z, Zhou Y, Hua Y, Guo J. Surgical treatment and prognosis of Borrmann type IIII (gastric cancer involving the whole stomach. Zhonghua Wei Chang Wai Ke Za Zhi 2018; 21: 185-189.
- Ilm K, Fuchs S, Mudduluru G, Stein U. MACC1 is post-trans¬criptionally regulated by miR-218 in colorectal cancer. Oncotarget 2016; 7: 53443-53458.
- Sitarz R, Skierucha M, Mielko J, Offerhaus GJA, Maciejewski R, Polkowski WP. Gastric cancer: epidemiology, prevention, classi¬fication, and treatment. Cancer Manage Res 2018; 10: 239-248.
- Stein U, Walther W, Arlt F, Schwabe H, Smith J, Fichtner I, Birchmeier W, Schlag PM. MACC1, a newly identified key regu¬lator of HGF-MET signaling, predicts colon cancer metastasis. Nat Med 2009; 15: 59-67.
- Zhang C, Li H, Wang J, Zhang J, Hou X. MicroRNA-338-3p suppresses cell proliferation, migration and invasion in human ma¬lignant melanoma by targeting MACC1. Exp Ther Med 2019; 18: 997-1004.
- Wang Y, Zhao M, Zhao H, Cheng S, Bai R, Song M. MicroR¬NA-940 restricts the expression of metastasis-associated gene MACC1 and enhances the antitumor effect of Anlotinib on colorec¬tal cancer. Onco Targets Ther 2019; 12: 2809-2822.
- Link T, Kuhlmann JD, Kobelt D, Herrmann P, Vassileva YD, Kramer M, Frank K, Gockenjan M, Wimberger P, Stein U. Clinical relevance of circulating MACC1 and S100A4 transcripts for ovarian cancer. Mol Oncol 2019; 13: 1268-1279.
- Li Z, Guo T, Fang L, Li N, Wang X, Wang P, Zhao S, Li F, Cui Y, Shu X, Zhao L, Li J, Gu C. MACC1 overexpression in carcinoma associated fibroblasts induces the invasion of lung adenocarcinoma cells via paracrine signaling. Int J Oncol 2019; 54: 1367-1375.
- Pan T, Chen W, Yuan X, Shen J, Qin C, Wang L. miR-944 inhi¬bits metastasis of gastric cancer by preventing the epithelial-mesen¬chymal transition viaMACC1/Met/AKT signaling. FEBS Open Bio 2017; 7: 905-914.
- Zhang K, Zhang Y, Zhu H, Xue N, Liu J, Shan C, Zhu Q. High expression of MACC1 predicts poor prognosis in patients with os¬teosarcoma. Tumor Biol 2014; 35: 1343-1350.
- Zhao Y, Dai C, Wang M, Kang H, Lin S, Yang P, Liu X, Liu K, Xu P, Zheng Y, Li, S, Dai Z. Clinicopathological and prognostic significance of metastasis-associated in colon cancer-1 (MACC1) overexpression in colorectal cancer: a meta-analysis. Oncotarget 2016; 7: 62966-62975.
- Kim JH, Kim SS, Lee JH, Jung DH, Cheung DY, Chung WC, Park S. H. Early detection is important to reduce the economic bur¬den of gastric cancer. J Gastric Cancer 2018; 18: 82-89.
- Isobe T, Hashimoto K, Kizaki J, Miyagi M, Aoyagi K, Koufuji K, Shirouzu K. Characteristics and prognosis of gastric cancer in young patients. Oncol Rep 2013; 30: 43-49.
- Fang N, Zhang HQ, He B, Xie M, Lu S, Wan YY, Wang NR. Clinicopathological characteristics and prognosis of gastric cancer with malignant ascites. Tumor Biol 2014; 35: 3261-3268.
- Saito H, Takaya S, Fukumoto Y, Osaki T, Tatebe S, Ikeguchi M. Clinicopathologic characteristics and prognosis of gastric cancer in young patient. Yonago Acta Med 2012; 55: 57-61.
- Liu G, Xu M, Gao T, Xu L, Zeng P, Bo H, Li F, Zhang W, Wang Z. Surgical Compliance and Outcomes in Gastric Cancer: a popula¬tion-based cohort study. J Cancer 2019; 10: 779-788.
- Zuo QS, Yan R, Feng DX, Zhao R, Chen C, Jiang YM, Cruz" Correa M, Casson AG, Kang XD, Han F, Chen T. Loss of imprin¬ting and abnormal expression of the insulin"like growth factor 2 gene in gastric cancer. Mol Carcinog 2011; 50: 390-396.
- Qu JH, Chang XJ, Lu YY, Bai WL, Chen Y, Zhou L, Zeng Z, Wang CP, An LJ, Hao LY, Xu GL, Gao XD, Lou M, Lv JY, Yang YP. Overexpression of metastasis-associated in colon cancer 1 predicts a poor outcome of hepatitis B virus-related hepatocellular carcinoma. World J Gastroenterol 2012; 18: 2995-3003.
- Yamak N, Yaykasli KO, Yilmaz U, Eroz R, Uzunlar AK, Ankaralı H, Sahiner C, Baltaci D. Association Between Survivin Gene Poly¬morphisms and the Susceptibility to Colon Cancer Development in Turkish Population, Asian Pac J Cancer Prev 2014; 15(20): 8963- 8967.
- Ge SH, Wu XJ, Wang XH, Xing XF, Zhang LH, Zhu YB, Du H, Dong B, Hu Y, Ji JF. Over-expression of metastasis-associated in colon cancer-1 (MACC1) associates with better prognosis of gastric cancer patients. Chin J Cancer Res 2011; 23: 153-159.
- Schmid F, Wang Q, Huska MR, Andrade-Navarro MA, Lemm M, Fichtner I, Dahlmann M, Kobelt D, Walther W, Smith J, Schlag PM, Stein U. SPON2, a newly identified target gene of MACC1, drives colorectal cancer metastasis in mice and is prognostic for colorectal cancer patient survival. Oncogene 2015; 35: 5942-5952.
- Kanda M, Sugimoto H, Kodera Y. Genetic and epigenetic aspects of initiation and progression of hepatocellular carcinoma. World J Gastroenterol 2015; 21: 10584-10597.
- Zhang Q, Xu P, Lu Y, Dou H. Correlation of MACC1/c-Myc Expression in Endometrial Carcinoma with Clinical/Pathological Features or Prognosis. Med Sci Monit 2018; 24: 4738-4744.
- Wang G, Kang MX, Lu WJ, Chen Y, Zhang B, Wu YL. MACC1: A potential molecule associated with pancreatic cancer metastasis and chemoresistance. Oncol Lett 2012; 4: 783-791.
- Guo L, Ou S, Ma X, Zhang S, Lai Y. MACC1 silencing inhibits cell proliferation and induces cell apoptosis of lung adenocarcinoma cells through the β-catenin pathway. Neoplasma 2018; 65: 552-560.
- Xu ST, Ding X, Ni QF, Ni QF, Jin SJ. Targeting MACC1 by RNA interference inhibits proliferation and invasion of bladder uro¬thelial carcinoma in T24 cells. Int J Clin Exp Pathol 2015; 8: 7937- 7944.
- Nie Y, Luo F, Wang L, Yang T, Shi L, Li X, Shen J, Xu W, Guo T and Lin Q: Anti-hyperlipidemic effect of rice bran polysaccharide and its potential mechanism in high-fat diet mice. Food Func 2017; 8(11): 4028-4041.
- Lou Y, Yang J, Wang L, Chen X, Xin X and Liu Y: The clini¬cal efficacy study of treatment to Chiari malformation type I with syringomyelia under the minimally invasive surgery of resection of Submeningeal cerebellar Tonsillar Herniation and reconstruction of Cisterna magna. Saudi J Biol Sci 2019; 26(8): 1927-1931.
- Wang L, Lin Q, Yang T, Liang Y, Nie Y, Luo Y and Luo F: Oryza¬nol modifies high fat diet-induced obesity, liver gene expression pro¬file, and inflammation response in mice. J Agri Food Chem 2017; 65(38): 8374-8385.
- Lou Y, Shi J, Guo D, Qureshi AK and Song L: Function of PD-L1 in antitumor immunity of glioma cells. Saudi J Boil Sci 2017; 24(4): 803-807.
- Lou Y, Guo D, Zhang H and Song L: Effectiveness of mesenchy¬mal stems cells cultured by hanging drop vs. conventional culturing on the repair of hypoxic-ischemic-damaged mouse brains, measured by stemness gene expression. Open Life Sci 2016; 11(1): 519-523.
- Liang Y, Lin Q, Huang P, Wang Y, Li J, Zhang L and Cao J: Rice Bioactive Peptide Binding with TLR4 To Overcome H2O2-Induced Injury in Human Umbilical Vein Endothelial Cells through NF-κB Signaling. J Agri Food Chem 2018; 66(2): 440-448.
- Wang L., Wu Y, Lin L, Liu P, Huang H, Liao W, Zheng D, Zuo Q, Sun L, Huang N, Shi M. Metastasis"associated in colon can-cer"1 upregulation predicts a poor prognosis of gastric cancer and promotes tumor cell proliferation and invasion. Int J Cancer 2013; 133(6):1419-1430.
- Guo T, Yang J, Yao J. Zhang Y, Da M, Duan,Y. Expression of MACC1 and c-Met in human gastric cancer and its clinical signifi¬cance. Cancer Cell Int 2013; 13(1): 121-126.
- Guo T, Lin Q, Li X, Nie Y, Wang L, Shi L and Luo F: Octacosa¬nol attenuates inflammation in both RAW264. 7 macrophages and a mouse model of colitis. J Agri Food Chem 2017; 65(18): 3647-3658.
- Li W, Jia MX, Wang JH, Lu JL, Deng J, Tang JX and Liu C: As¬sociation of MMP9-1562C/T and MMP13-77A/G polymorphisms with non-small cell lung cancer in southern Chinese population. Biomol 2019; 9(3): 107-119.
- Nie Y, Luo F and Lin Q: Dietary nutrition and gut microflora: A promising target for treating diseases. Trends Food Sci Technol 2018;75: 72-80.
- Ren Y, Jiao X and Zhang L: Expression level of fibroblast growth factor 5 (FGF5) in the peripheral blood of primary hypertension and its clinical significance. Saudi J Biol Sci 2018; 25(3): 469-473.
- Chen X, Xu Y, Meng L, Chen X, Yuan L, Cai Q, Shi W and Huang G: Non-parametric partial least squares–discriminant analy¬sis model based on sum of ranking difference algorithm for tea grade identification using electronic tongue data identify tea grade using e-tongue data. Sens Actuators B Chem 2020; 127924.
References
Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of inci¬dence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 2018; 68(6): 394-424.
Chen W, Zheng R, Baade PD, Zhang S, Zeng H, Bray F, Jemal A, Yu HQ, He, J. Cancer statistics in China, 2015. CA Cancer J Clin 2016; 66(2): 115-132.
Dong R, Zhang Z, Zhou Y, Hua Y, Guo J. Surgical treatment and prognosis of Borrmann type IIII (gastric cancer involving the whole stomach. Zhonghua Wei Chang Wai Ke Za Zhi 2018; 21: 185-189.
Ilm K, Fuchs S, Mudduluru G, Stein U. MACC1 is post-trans¬criptionally regulated by miR-218 in colorectal cancer. Oncotarget 2016; 7: 53443-53458.
Sitarz R, Skierucha M, Mielko J, Offerhaus GJA, Maciejewski R, Polkowski WP. Gastric cancer: epidemiology, prevention, classi¬fication, and treatment. Cancer Manage Res 2018; 10: 239-248.
Stein U, Walther W, Arlt F, Schwabe H, Smith J, Fichtner I, Birchmeier W, Schlag PM. MACC1, a newly identified key regu¬lator of HGF-MET signaling, predicts colon cancer metastasis. Nat Med 2009; 15: 59-67.
Zhang C, Li H, Wang J, Zhang J, Hou X. MicroRNA-338-3p suppresses cell proliferation, migration and invasion in human ma¬lignant melanoma by targeting MACC1. Exp Ther Med 2019; 18: 997-1004.
Wang Y, Zhao M, Zhao H, Cheng S, Bai R, Song M. MicroR¬NA-940 restricts the expression of metastasis-associated gene MACC1 and enhances the antitumor effect of Anlotinib on colorec¬tal cancer. Onco Targets Ther 2019; 12: 2809-2822.
Link T, Kuhlmann JD, Kobelt D, Herrmann P, Vassileva YD, Kramer M, Frank K, Gockenjan M, Wimberger P, Stein U. Clinical relevance of circulating MACC1 and S100A4 transcripts for ovarian cancer. Mol Oncol 2019; 13: 1268-1279.
Li Z, Guo T, Fang L, Li N, Wang X, Wang P, Zhao S, Li F, Cui Y, Shu X, Zhao L, Li J, Gu C. MACC1 overexpression in carcinoma associated fibroblasts induces the invasion of lung adenocarcinoma cells via paracrine signaling. Int J Oncol 2019; 54: 1367-1375.
Pan T, Chen W, Yuan X, Shen J, Qin C, Wang L. miR-944 inhi¬bits metastasis of gastric cancer by preventing the epithelial-mesen¬chymal transition viaMACC1/Met/AKT signaling. FEBS Open Bio 2017; 7: 905-914.
Zhang K, Zhang Y, Zhu H, Xue N, Liu J, Shan C, Zhu Q. High expression of MACC1 predicts poor prognosis in patients with os¬teosarcoma. Tumor Biol 2014; 35: 1343-1350.
Zhao Y, Dai C, Wang M, Kang H, Lin S, Yang P, Liu X, Liu K, Xu P, Zheng Y, Li, S, Dai Z. Clinicopathological and prognostic significance of metastasis-associated in colon cancer-1 (MACC1) overexpression in colorectal cancer: a meta-analysis. Oncotarget 2016; 7: 62966-62975.
Kim JH, Kim SS, Lee JH, Jung DH, Cheung DY, Chung WC, Park S. H. Early detection is important to reduce the economic bur¬den of gastric cancer. J Gastric Cancer 2018; 18: 82-89.
Isobe T, Hashimoto K, Kizaki J, Miyagi M, Aoyagi K, Koufuji K, Shirouzu K. Characteristics and prognosis of gastric cancer in young patients. Oncol Rep 2013; 30: 43-49.
Fang N, Zhang HQ, He B, Xie M, Lu S, Wan YY, Wang NR. Clinicopathological characteristics and prognosis of gastric cancer with malignant ascites. Tumor Biol 2014; 35: 3261-3268.
Saito H, Takaya S, Fukumoto Y, Osaki T, Tatebe S, Ikeguchi M. Clinicopathologic characteristics and prognosis of gastric cancer in young patient. Yonago Acta Med 2012; 55: 57-61.
Liu G, Xu M, Gao T, Xu L, Zeng P, Bo H, Li F, Zhang W, Wang Z. Surgical Compliance and Outcomes in Gastric Cancer: a popula¬tion-based cohort study. J Cancer 2019; 10: 779-788.
Zuo QS, Yan R, Feng DX, Zhao R, Chen C, Jiang YM, Cruz" Correa M, Casson AG, Kang XD, Han F, Chen T. Loss of imprin¬ting and abnormal expression of the insulin"like growth factor 2 gene in gastric cancer. Mol Carcinog 2011; 50: 390-396.
Qu JH, Chang XJ, Lu YY, Bai WL, Chen Y, Zhou L, Zeng Z, Wang CP, An LJ, Hao LY, Xu GL, Gao XD, Lou M, Lv JY, Yang YP. Overexpression of metastasis-associated in colon cancer 1 predicts a poor outcome of hepatitis B virus-related hepatocellular carcinoma. World J Gastroenterol 2012; 18: 2995-3003.
Yamak N, Yaykasli KO, Yilmaz U, Eroz R, Uzunlar AK, Ankaralı H, Sahiner C, Baltaci D. Association Between Survivin Gene Poly¬morphisms and the Susceptibility to Colon Cancer Development in Turkish Population, Asian Pac J Cancer Prev 2014; 15(20): 8963- 8967.
Ge SH, Wu XJ, Wang XH, Xing XF, Zhang LH, Zhu YB, Du H, Dong B, Hu Y, Ji JF. Over-expression of metastasis-associated in colon cancer-1 (MACC1) associates with better prognosis of gastric cancer patients. Chin J Cancer Res 2011; 23: 153-159.
Schmid F, Wang Q, Huska MR, Andrade-Navarro MA, Lemm M, Fichtner I, Dahlmann M, Kobelt D, Walther W, Smith J, Schlag PM, Stein U. SPON2, a newly identified target gene of MACC1, drives colorectal cancer metastasis in mice and is prognostic for colorectal cancer patient survival. Oncogene 2015; 35: 5942-5952.
Kanda M, Sugimoto H, Kodera Y. Genetic and epigenetic aspects of initiation and progression of hepatocellular carcinoma. World J Gastroenterol 2015; 21: 10584-10597.
Zhang Q, Xu P, Lu Y, Dou H. Correlation of MACC1/c-Myc Expression in Endometrial Carcinoma with Clinical/Pathological Features or Prognosis. Med Sci Monit 2018; 24: 4738-4744.
Wang G, Kang MX, Lu WJ, Chen Y, Zhang B, Wu YL. MACC1: A potential molecule associated with pancreatic cancer metastasis and chemoresistance. Oncol Lett 2012; 4: 783-791.
Guo L, Ou S, Ma X, Zhang S, Lai Y. MACC1 silencing inhibits cell proliferation and induces cell apoptosis of lung adenocarcinoma cells through the β-catenin pathway. Neoplasma 2018; 65: 552-560.
Xu ST, Ding X, Ni QF, Ni QF, Jin SJ. Targeting MACC1 by RNA interference inhibits proliferation and invasion of bladder uro¬thelial carcinoma in T24 cells. Int J Clin Exp Pathol 2015; 8: 7937- 7944.
Nie Y, Luo F, Wang L, Yang T, Shi L, Li X, Shen J, Xu W, Guo T and Lin Q: Anti-hyperlipidemic effect of rice bran polysaccharide and its potential mechanism in high-fat diet mice. Food Func 2017; 8(11): 4028-4041.
Lou Y, Yang J, Wang L, Chen X, Xin X and Liu Y: The clini¬cal efficacy study of treatment to Chiari malformation type I with syringomyelia under the minimally invasive surgery of resection of Submeningeal cerebellar Tonsillar Herniation and reconstruction of Cisterna magna. Saudi J Biol Sci 2019; 26(8): 1927-1931.
Wang L, Lin Q, Yang T, Liang Y, Nie Y, Luo Y and Luo F: Oryza¬nol modifies high fat diet-induced obesity, liver gene expression pro¬file, and inflammation response in mice. J Agri Food Chem 2017; 65(38): 8374-8385.
Lou Y, Shi J, Guo D, Qureshi AK and Song L: Function of PD-L1 in antitumor immunity of glioma cells. Saudi J Boil Sci 2017; 24(4): 803-807.
Lou Y, Guo D, Zhang H and Song L: Effectiveness of mesenchy¬mal stems cells cultured by hanging drop vs. conventional culturing on the repair of hypoxic-ischemic-damaged mouse brains, measured by stemness gene expression. Open Life Sci 2016; 11(1): 519-523.
Liang Y, Lin Q, Huang P, Wang Y, Li J, Zhang L and Cao J: Rice Bioactive Peptide Binding with TLR4 To Overcome H2O2-Induced Injury in Human Umbilical Vein Endothelial Cells through NF-κB Signaling. J Agri Food Chem 2018; 66(2): 440-448.
Wang L., Wu Y, Lin L, Liu P, Huang H, Liao W, Zheng D, Zuo Q, Sun L, Huang N, Shi M. Metastasis"associated in colon can-cer"1 upregulation predicts a poor prognosis of gastric cancer and promotes tumor cell proliferation and invasion. Int J Cancer 2013; 133(6):1419-1430.
Guo T, Yang J, Yao J. Zhang Y, Da M, Duan,Y. Expression of MACC1 and c-Met in human gastric cancer and its clinical signifi¬cance. Cancer Cell Int 2013; 13(1): 121-126.
Guo T, Lin Q, Li X, Nie Y, Wang L, Shi L and Luo F: Octacosa¬nol attenuates inflammation in both RAW264. 7 macrophages and a mouse model of colitis. J Agri Food Chem 2017; 65(18): 3647-3658.
Li W, Jia MX, Wang JH, Lu JL, Deng J, Tang JX and Liu C: As¬sociation of MMP9-1562C/T and MMP13-77A/G polymorphisms with non-small cell lung cancer in southern Chinese population. Biomol 2019; 9(3): 107-119.
Nie Y, Luo F and Lin Q: Dietary nutrition and gut microflora: A promising target for treating diseases. Trends Food Sci Technol 2018;75: 72-80.
Ren Y, Jiao X and Zhang L: Expression level of fibroblast growth factor 5 (FGF5) in the peripheral blood of primary hypertension and its clinical significance. Saudi J Biol Sci 2018; 25(3): 469-473.
Chen X, Xu Y, Meng L, Chen X, Yuan L, Cai Q, Shi W and Huang G: Non-parametric partial least squares–discriminant analy¬sis model based on sum of ranking difference algorithm for tea grade identification using electronic tongue data identify tea grade using e-tongue data. Sens Actuators B Chem 2020; 127924.