高尔基体磷蛋白3在结直肠癌组织中表达及其对结直肠癌细胞增殖、侵袭和迁移的影响

刘师宏 汪威 穆小松

解剖学报 ›› 2018, Vol. 49 ›› Issue (4) : 461-468.

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解剖学报 ›› 2018, Vol. 49 ›› Issue (4) : 461-468. DOI: 10.16098/j.issn.0529-1356.2018.04.008
肿瘤生物学

高尔基体磷蛋白3在结直肠癌组织中表达及其对结直肠癌细胞增殖、侵袭和迁移的影响

  • 刘师宏1 汪威2 穆小松1*
作者信息 +

Expression of Golgi phosphoprotein 3 in colorectal cancer tissues and its effects on proliferation, invasion and migration of colorectal cancer cells

  • LIU Shi-hong1 WANG Wei2 MU Xiao-song 1*
Author information +
文章历史 +

摘要

目的  分析高尔基体磷蛋白3(GOLPH3)在结直肠癌组织中的表达情况,及其对结直肠癌细胞增殖、侵袭和迁移的影响。方法  收集术前未经放、化疗治疗,经手术切除患者的结直肠癌组织及其相应的癌旁组织(40例);采用免疫组织化学法检测组织中GOLPH3的表达,分析GOLPH3与结直肠癌临床病理特征的关系;构建稳定沉默GOLPH3的结直肠癌细胞株,并设立阴性对照组和空白对照组,Western blotting法检测3组细胞中GOLPH3蛋白的表达,MTT法检测3组细胞的增殖活性,Transwell实验分别检测3组细胞的侵袭和迁移能力。结果  GOLPH3在癌组织中主要为阳性表达,且阳性表达率(65.0%)显著高于癌旁组织(35.0%)(P<0.05);GOLPH3在TNM分期为Ⅲ~Ⅳ期、浸润深度≥2 cm、中低分化及有淋巴结转移的癌组织中的阳性表达率明显高于TNM分期Ⅰ~Ⅱ期、浸润深度<2 cm、高分化及无淋巴结转移的癌组织(P<0.05)。与阴性对照组和空白对照组比,基因沉默组GOLPH3蛋白表达量、细胞增殖活性、侵袭能力及迁移能力均明显降低(P<0.05)。结论 GOLPH3在结直肠癌组织中高表达,其表达与肿瘤分期、侵袭深度、分化程度及淋巴结转移有关,抑制GOLPH3基因表达可下调GOLPH3蛋白表达,抑制结直肠癌细胞增殖、侵袭和迁移。

Abstract

Objective  To analyze the expression of Golgi phosphoprotein 3 (GOLPH3) in colorectal cancer tissues and its influence on the proliferation, invasion and migration of colorectal cancer cells. Methods  The colorectal cancer tissues and paracancerous tissues were collected from the surgically resected colorectal cancer patients (40 cases) without radiotherapy or chemotherapy before the operation. The expression of GOLPH3 in the colorectal cancer tissues and paracancerous tissues were detected by immunohistochemistry, and the relationship between GOLPH3 and clinicopathological features of colorectal cancer was analyzed. Colorectal cancer cell starin with GOLPH3 stable silent was constructed, and a negative control group and blank control group were established. The expression of GOLPH3 protein of cells in the three groups was detected by Western blotting. MTT assay was used to detect the proliferative activity of cells in the three groups. The invasion ability and migration ability of cells in the three groups were detected by transwell test. Results  The expression of GOLPH3 was mainly positive in the cancer tissue sample, and the positive expression rate (65.0%) of the cancer tissues was significantly higher than that of the paracancerous tissues (35.0%) (P<0.05). The GOLPH3 positive expression rate of cancer tissues with TNM stage Ⅲ-Ⅳ, invasion depth≥2 cm, middle-low differentiation and lymphatic metastasis were significantly higher than that of cancer tissues with TNM stageⅠ-Ⅱ, invasion depth<2 cm and high differentiation and without lymphatic metastasis (P<0.05). Compared with the negative control group and the blank control group, the expression level of GOLPH3, the cell proliferation activity, the invasion ability and migration ability rate in the gene silencing group were significantly lower (P<0.05). Conclusion  GOLPH3 is highly expressed in the colorectal cancer tissues, and the expression level is related to the tumor staging, invasion depth, differentiation and lymphatic metastasis. Inhibiting the expression of GOLPH3 gene could deregulate the GOLPH3 protein level, and inhibit the proliferation, invasion and migration of colorectal cancer cells.

关键词

结直肠癌 / 高尔基体磷蛋白3 / 基因沉默 / 细胞增殖 / 免疫组织化学 /

Key words

 Colorectal cancer / Golgi phosphoprotein 3 / Gene silencing / Cell proliferation / Immunohistochemistry / Human

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刘师宏 汪威 穆小松. 高尔基体磷蛋白3在结直肠癌组织中表达及其对结直肠癌细胞增殖、侵袭和迁移的影响[J]. 解剖学报. 2018, 49(4): 461-468 https://doi.org/10.16098/j.issn.0529-1356.2018.04.008
LIU Shi-hong WANG Wei MU Xiao-song. Expression of Golgi phosphoprotein 3 in colorectal cancer tissues and its effects on proliferation, invasion and migration of colorectal cancer cells[J]. Acta Anatomica Sinica. 2018, 49(4): 461-468 https://doi.org/10.16098/j.issn.0529-1356.2018.04.008

参考文献

[1] Li DJ, Li Q, He YT. Epidemiological trends of colorectal cancer [J]. Cancer Research on Prevention and Treatment, 2015, 42(3):305-310. (in Chinese)
李道娟, 李倩, 贺宇彤. 结直肠癌流行病学趋势[J]. 肿瘤防治研究, 2015, 42(3):305-310.
[2] Shen YCh, Shi YK, Han XH. Research progress on targeted therapy for colorected cancer[J]. Chinese Journal of Pathology, 2015, 44(6): 430-433. (in Chinese)
沈胤晨, 石远凯, 韩晓红. 结直肠癌靶向治疗研究进展[J]. 中华病理学杂志, 2015, 44(6):430-433.
[3] Xu LL, An GY. Reearch progress on targeted therapy for advanced coloretal cancer [J]. Cancer Progress, 2014, 12(2):117-121.  (in Chinese)
徐伶玲, 安广宇. 晚期结直肠癌靶向治疗研究进展[J]. 癌症进展, 2014, 12(2):117-121.
[4] Moriarity A, O’Sullivan J, Kennedy J, et al. Current targeted therapies in the treatment of advanced colorectal cancer: a review [J]. Ther Adv Med Oncol, 2016, 8(4):276-293.
[5] Zhou B, Wang G, Gao S, et al. Expression of GOLPH3 protein in colon cancer tissues and its association with the prognosis of patients [J]. Oncol Lett, 2016, 12(5):3936-3940.
[6] Zeng Z, Lin H, Zhao X, et al. Overexpression of GOLPH3 promotes proliferation and tumorigenicity in breast cancer via suppression of the FOXO1 transcription factor[J]. Clin Cancer Rese, 2012, 18(15):4059-4069.
[7] Zhang YX, Zhao HJ, Song WG, et al. Effects of TWEAK antisense oligonucleotide on the proliferation and invasive capability of the human colon cancer cell line SW480 [J]. Acta Anatomica Sinica, 2014, 45(1):74-79. (in Chinese)
张延新, 赵红军, 宋文刚, 等. TWEAK反义寡核苷酸对人结肠癌细胞系SW480增殖及侵袭能力的影响[J]. 解剖学报, 2014, 45(1):74-79.
[8] Shu XJ. Expression of Lgr5 in the colon cancer tissues and its transfer promoting role [J]. Journal of Hainan Medical College, 2016, 22(9):833-835. (in Chinese)
舒新军. Lgr5在结肠癌组织中的表达及促进转移的临床研究[J]. 海南医学院学报, 2016, 22(9):833-835.
[9] Scott KL, Kabbarah O, Liang MC, et al. GOLPH3 modulates mTOR signalling and rapamycin sensitivity in cancer [J]. Nature, 2009, 459(7250):1085-1090.
[10] Liao HH, Li JH, Wang KB, et al. Expression of GOLPH3 and the relationship with clinical pathological features in esopha-geal carcinoma [J]. Journal of Modern Oncology, 2014, 22(9):2112-2114. (in Chinese)
廖和和, 李俊海, 王凯斌, 等. GOLPH3蛋白在食管癌中的表达及临床意义[J]. 现代肿瘤医学, 2014, 22(9):2112-2114.
[11] Yang W, Du PM, Niu Q. Expression of GOLPH3 in gastric cancer and its clinical significance [J]. Journal of Practical Oncology, 2015, 30(2):171-175. (in Chinese)
杨威, 杜朋明, 牛强. 胃癌组织中GOLPH3的表达及临床意义[J]. 实用肿瘤杂志, 2015, 30(2):171-175.
[12] Tang JL, Wen XN, Bai J. Expression of GOLPH3 in NSCLC and Its Prognostic Significance [J]. Journal of Medical Research, 2015, 44(2):126-130. (in Chinese)
唐纪兰, 文新年, 白晶. GOLPH3在非小细胞肺癌组织中的表达及其与预后的关系[J]. 医学研究杂志, 2015, 44(2):126-130.
[13] Zhang ChSh, Chen BM, Jiao A, et al. Expression of Golgi phosphoprotein 3 in human hepatocellular carcinoma and its clinicopathological significance [J]. Journal of China Medical University, 2017, 46(3):214-218. (in Chinese)
张城硕, 陈保民, 焦奥, 等. 高尔基体磷蛋白3在肝细胞癌中的表达特点及其临床病理学意义[J]. 中国医科大学学报, 2017, 46(3):214-218.
[14] Duan K, Li YY, Zhao Y, et al. Expression dn significance of Golgi phosphoprotein 3 in prostate cancer[J]. Journal of Practical Medicine, 2016, 32(12): 2004-2006. (in Chinese)
段堃, 李岩岩, 赵艳, 等. 高尔基体磷蛋白3在前列腺癌中的表达及意义[J]. 实用医学杂志, 2016, 32(12):2004-2006.
[15] Buschman MD, Rahajeng J, Field SJ. GOLPH3 Links the Golgi, DNA Damage, and Cancer [J]. Cancer Res, 2015, 75(4):624-627.
[16] Yang XF, Qiu ChZh, Wang ChX, et al. Relationship between golgi phosphorylation protein3 expression and prognosis in colorectal cancer [J]. Chinese Journal of General Surgery, 2014, 23(10):1362-1366. (in Chinese)
杨晓峰, 邱成志, 王春晓, 等. 高尔基磷酸化蛋白3在结直肠癌中的表达与预后的关系[J]. 中国普通外科杂志, 2014, 23(10):1362-1366.
[17] Yu WSh, Qiu ChZh, Wang ChX, et al. Golph3 expression and apoptosis in colorectal cancer cells [J]. Chinese Journal of Clinical Oncology, 2013(18):1094-1097. (in Chinese)
余外市, 邱成志, 王春晓, 等. 结直肠癌组织中Golph3的表达与细胞凋亡的相关性[J]. 中国肿瘤临床, 2013(18):1094-1097.
[18] Farber-Katz S, Dippold H, Buschman M, et al. DNA damage triggers Golgi dispersal via DNA-PK and GOLPH3 [J]. J Int Oncol, 2014, 156(3):413-427.
[19] Lin YP, Li H, Shen LD. Expression and role of Golgi phosphoprotein 3 in cancer [J]. J Int Oncol, 2017, 44(1):27-30.  (in Chinese)
林艳苹, 李宏, 沈丽达. 高尔基体磷蛋白3在肿瘤中的表达及作用[J]. 国际肿瘤学杂志, 2017, 44(1):27-30.
[20] Chin KL, Chin L. Signaling from the Golgi: mechanisms and models for Golgi phosphoprotein 3-mediated oncogenesis [J]. Clin Cancer Res, 2010, 16(8):2229-2234.
[21] Xing M, Peterman MC, Davis RL, et al. GOLPH3 drives cell migration by promoting Golgi reorientation and directional trafficking to the leading edge [J]. Mol Biol Cell, 2016,27(24):3828-3840.
[22] Zhang X, Ding Z, Mo J, et al. GOLPH3 promotes glioblastoma cell migration and invasion via the mTOR-YB1 pathway in vitro [J]. Mol Carcinog, 2015, 54(11):1252-1263.

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