Expression of miR-145 in Gastric Cancer and Lymph Nodes Tissues and Its Clinical Association

doi:10.3969/j.issn.1007-9572.2016.29.010

Abstract

Abstract: Background　MicroRNAs have been reported as key regulators of various cancers，and miR-145 is one of these microRNAs.However，the mechanism and clinical significance of miR-145 in metastases of gastric cancer remain unknown.Objective　To detect the expression of miR-145，matrix metalloproteinase 9（MMP-9），matrix metalloproteinase inhibitor 1（TIMP-1）in gastric cancer tissues，adjacent normal tissues and metastatic lymph node，non-metastatic lymph nodes tissues and explore the expression and clinical significance of miR-145 in gastric cancer tissues.Methods　From January 2014 to October 2015，120 patients with gastric cancer were included in the study，who accepted radical gastrectomy in Third Department of Surgery of the Fourth Hospital of Hebei Medical University.The expression of miR-145，MMP-9，TIMP-1 mRNA were examined in gastric cancer tissues，adjacent normal tissues and metastatic lymph node，non-metastatic lymph nodes tissues used quantitative real time polymerase chain reaction（qPCR）.Results　There were statistically significant difference in the expressions of miR-145，MMP-9,TIMP-1 mRNA in gastric cancer tissues，adjacent normal tissues and metastatic lymph node，non-metastatic lymph nodes tissues（P<0.001）.The expressions of miR-145，TIMP-1 mRNA in adjacent normal tissues were higher than gastric cancer tissues，and the expression of MMP-9 mRNA in adjacent normal tissues was lower than gastric cancer tissues（P<0.05）.The expression of miR-145 mRNA in non-metastatic lymph nodes tissues was lower than gastric cancer tissues and adjacent normal tissues.The expressions of MMP-9 mRNA in non-metastatic lymph nodes tissues was lower than gastric cancer tissues.The expression of TIMP-1 mRNA in non-metastatic lymph nodes tissues was higher than gastric cancer tissues.The expression of miR-145，TIMP-1 mRNA in metastatic lymph node tissues were lower than gastric cancer tissues，adjacent normal tissues and non-metastatic lymph nodes tissues.The expressions of MMP-9 mRNA in metastatic lymph nodes was higher than gastric cancer tissues，adjacent normal tissues and non-metastatic lymph nodes tissues（P<0.05）.A positive relationship was found between the expression of miR-145 mRNA in gastric cancer tissues and adjacent normal tissues（rs=0.302，P<0.001）.A positive relationship was found between the expressions of miR-145 mRNA in metastatic lymph node tissues and their corresponding gastric cancer tissues（rs=0.346，P=0.003）.There was no relationship between the expressions of miR-145 mRNA in non-metastatic lymph nodes tissues and their corresponding gastric cancer tissues（rs=0.264，P=0.070）.A negative relationship was found between the expressions of miR-145 and MMP-9 mRNA in gastric cancer tissues（rs=-0.403，P<0.001）.A positive relationship was found between the expressions of miR-145 and TIMP-1 mRNA in gastric cancer tissues（rs=0.294，P=0.001）.A negative relationship was found between the expressions of miR-145 and MMP-9 mRNA in metastatic lymph node tissues（rs=-0.323，P<0.001）.There was no relationship between the expressions of miR-145 and TIMP-1 mRNA in metastatic lymph node tissues（rs=0.165，P=0.072）.There were no relationship between the expressions of miR-145 and MMP-9，TIMP-1 mRNA in non-metastatic lymph nodes tissues（rs=-0.119，P=0.197；rs=0.096，P=0.295）.Conclusion　The expression of miR-145 mRNA was significantly down-regulated in gastric cancer and lymph nodes tissues.The miR-145 might be involved in metastases of gastric cancer by regulating MMPs family.

Key words: Stomach neoplasms, MicroRNAs, Neoplasm metastasis

摘要： 背景　研究发现微小RNA（miR）在肿瘤调控方面发挥了重要作用，但miR-145在胃癌转移中的作用尚不明确。目的　检测miR-145、基质金属蛋白酶9（MMP-9）、基质金属蛋白酶抑制剂1（TIMP-1）在胃癌组织、癌旁组织及转移淋巴结、非转移淋巴结组织中的表达水平，探讨miR-145在胃癌组织中的表达水平及其临床意义。方法　选取2014年1月—2015年10月于河北医科大学第四医院外三科住院并行胃癌根治术的患者120例，肿瘤标本切除后取胃癌组织、癌旁组织、淋巴结组织，采用实时荧光定量聚合酶链反应（qPCR）检测胃癌组织、癌旁组织、非转移淋巴结组织、转移淋巴结组织miR-145、MMP-9、TIMP-1 mRNA表达水平。结果　胃癌组织、癌旁组织、非转移淋巴结、转移淋巴结组织miR-145、MMP-9、TIMP-1 mRNA表达水平比较，差异均有统计学意义（P<0.001）；其中癌旁组织miR-145、TIMP-1 mRNA表达水平高于胃癌组织，MMP-9 mRNA表达水平低于胃癌组织；非转移淋巴结组织miR-145 mRNA表达水平低于胃癌组织和癌旁组织，MMP-9 mRNA表达水平低于胃癌组织，TIMP-1 mRNA表达水平高于胃癌组织；转移淋巴结组织miR-145、TIMP-1 mRNA表达水平低于胃癌组织、癌旁组织和非转移淋巴结组织，MMP-9 mRNA表达水平高于胃癌组织、癌旁组织和非转移淋巴结组织（P<0.05）。胃癌组织miR-145 mRNA表达水平与癌旁组织呈正相关（rs=0.302，P<0.001），转移淋巴结组织miR-145 mRNA表达水平与配对胃癌组织呈正相关（rs=0.346，P=0.003），非转移淋巴结组织miR-145 mRNA表达水平与配对胃癌组织无线性相关关系（rs=0.264，P=0.070）。胃癌组织miR-145 mRNA表达水平与MMP-9 mRNA表达水平呈负相关（rs=-0.403，P<0.001），与TIMP-1 mRNA表达水平呈正相关（rs=0.294，P=0.001）；转移淋巴结组织miR-145 mRNA表达水平与MMP-9 mRNA表达水平呈负相关（rs=-0.323，P<0.001），与TIMP-1 mRNA表达水平无线性相关关系（rs=0.165，P=0.072）；非转移淋巴结组织miR-145 mRNA表达水平与MMP-9、TIMP-1 mRNA表达水平无线性相关关系（rs=-0.119，P=0.197；rs=0.096，P=0.295）。结论　miR-145在胃癌组织及淋巴结组织中表达明显下调，miR-145可能通过调节MMPs家族成员而参与胃癌转移。

关键词: 胃肿瘤, 微RNAs, 肿瘤转移

WANG Li-li, LI Yong, TAN Bi-bo, FAN Li-qiao, ZHAO Qun, WANG Dong, LIU Yu, LIU Qing-wei. Expression of miR-145 in Gastric Cancer and Lymph Nodes Tissues and Its Clinical Association[J]. Chinese General Practice, 2016, 19(29): 3558-3561.

王力利, 李勇, 檀碧波, 范立侨, 赵群, 王冬, 刘羽, 刘庆伟. 胃癌及淋巴结组织中miR-145的表达水平及其临床意义研究[J]. 中国全科医学, 2016, 19(29): 3558-3561.

References

［1］ARA H，TAKAGISHI M，ENOMOTO A，et al.Role for Daple in non-canonical Wnt signaling during gastric cancer invasion and metastasis［J］.Cancer Sci，2016，107（2）：133-139. ［2］LI Z，YU X，WANG Y，et al.By downregulating TIAM1 expression，microRNA-329 suppresses gastric cancer invasion and growth［J］.Oncotarget，2015，6（19）：17559-17569. ［3］LIU L，YE J X，QIN Y Z，et al.Evaluation of miR-29c，miR-124，miR-135a and miR-148a in predicting lymph node metastasis and tumor stage of gastric cancer［J］.Int J Clin Exp Med，2015，8（12）：22227-22236. ［4］LIU H，GAO Y，SONG D，et al.Correlation between microRNA-421 expression level and prognosis of gastric cancer［J］.Int J Clin Exp Pathol，2015，8（11）：15128-15132. ［5］CHEN W Q，HU L，CHEN G X，et al.Role of microRNA-7 in digestive system malignancy［J］.World J Gastrointest Oncol，2016，8（1）：121-127. ［6］CHEN R，CHEN S，LIAO J，et al.miR-145 facilitates proliferation and migration of endothelial progenitor cells and recanalization of arterial thrombosis in cerebral infarction mice via JNK signal pathway［J］.Int J Clin Exp Pathol，2015，8（10）：13770-13776. ［7］CUI X B，LI S，LI T T，et al.Targeting oncogenic PLCE1 by miR-145 impairs tumor proliferation and metastasis of esophageal squamous cell carcinoma［J］.Oncotarget，2016，7（2）：1777-1795. ［8］SHELYGIN Y A，SHUBIN V P，FROLOV S A，et al.The analysis of microRNAs miR-200C and miR-145 expression in colorectal cancer of different molecular subtypes［J］.Dokl Biochem Biophys，2015，463：243-246. ［9］权继传，解亦斌，田艳涛.国际抗癌联盟胃癌TNM分期系统第七版解读［J］.中华诊断学电子杂志，2014，2（1）：72-74. ［10］BGER C，BEHRENS H M，RCKEN C.Ki67-an unsuitable marker of gastric cancer prognosis unmasks intratumoral heterogeneity［J］.J Surg Oncol，2016，113（1）：46-54. ［11］LI C，DENG L，ZHI Q，et al.MicroRNA-183 functions as an oncogene by regulating PDCD4 in gastric cancer［J］.Anticancer Agents Med Chem，2016，16（4）：447-455. ［12］WU F，HUANG W，WANG X.microRNA-18a regulates gastric carcinoma cell apoptosis and invasion by suppressing hypoxia-inducible factor-1α expression［J］.Exp Ther Med，2015，10（2）：717-722. ［13］XU X，ZHANG Y，LIU Z，et al.miRNA-532-5p functions as an oncogenic microRNA in human gastric cancer by directly targeting RUNX3［J］.J Cell Mol Med，2016，20（1）：95-103. ［14］刘水逸，吴唐维，李晓怡，等.MicroRNA-145在乳腺癌中的表达及其对乳腺癌侵袭转移的影响［J］.中华检验医学杂志，2015，38（9）：613-616. ［15］赵一奇，焦峰，闵波，等.贲门癌miRNA-145的表达［J］.现代肿瘤医学，2016，24（6）：891-893. ［16］SALEM N，KAMAL I，AL-MAGHRABI J，et al.High expression of matrix metalloproteinases：MMP-2 and MMP-9 predicts poor survival outcome in colorectal carcinoma［J］.Future Oncol，2016，12（3）：323-331. ［17］FAN H，JIANG W，LI H，et al.MMP-1/2 and TIMP-1/2 expression levels，and the levels of collagenous and elastic fibers correlate with disease progression in a hamster model of tongue cancer［J］.Oncol Lett，2016，11（1）：63-68.

[1]	NONG Jingtang, YANG Chengmin, MO Shenglong, LU Zhicheng, TANG Lina, JIAN Chongdong, SHANG Jingwei. Research Progress on Prognostic Biomarkers after Cerebral Infarction: Mechanisms and Clinical Applications [J]. Chinese General Practice, 2025, 28(29): 3711-3720.
[2]	JIANG Xiaoman, XU Xinyi, DING Lingyu, GUO Yinning, MIAO Xueyi, CHEN Li, XU Qin. Clinical Characteristics and Correlation between Preoperative Frailty and Metabolic Syndrome among Older Patients with Gastric Cancer [J]. Chinese General Practice, 2025, 28(17): 2134-2141.
[3]	MA Guifen, ZHANG Qian, SUN Jing. Interpretation of the Key Updates in the Latest Version of 2024 NCCN Clinical Practice Guidelines for Gastric Cancer [J]. Chinese General Practice, 2025, 28(14): 1681-1688.
[4]	ZOU Yanling, WANG Xiaoqing, LI Xun, ZHANG Ziyan, LI Yi, YANG Lihua, GAO Juan, GUAN Huiyun, DUAN Peibei. Analysis of Gastrointestinal Core Symptoms and Influencing Factors in Postoperative Chemotherapy Patients with Gastric Cancer [J]. Chinese General Practice, 2024, 27(29): 3641-3647.
[5]	KANG Yinnan, SHI Jiaqi, WANG Junke, LI Bin, LI Chuyi, MA Jun, YU Xiaohui. Advances in the Application of Antibody Drug Conjugate in Gastric Cancer with Low Expression of Human Epidermal Growth Factor Receptor 2 [J]. Chinese General Practice, 2024, 27(18): 2287-2294.
[6]	MA Guifen, ZHANG Qian, LIU Juan, SUN Jing, LIN Genlai. Risk Factors Analysis of Long-term Prognosis in Patients with D2 Radical Surgery for Stage Ⅲ Gastric Cancer after Adjuvant Chemoradiotherapy: Based on the Data of 10-year Follow-up [J]. Chinese General Practice, 2024, 27(17): 2091-2097.
[7]	BAI Xin, WU Xinyu, ZHAO Zun, LIU Shuxin, LIU Simiao, XUE Yuhang, XU Junling, GAO Yongju. Efficacy Analysis of ¹³¹I Therapy in Serum Thyroglobulin Antibody Positive Differentiated Thyroid Carcinoma with Distant Metastasis [J]. Chinese General Practice, 2024, 27(15): 1833-1837.
[8]	WEN Jing, ZHANG Yue, LIANG Xuyang, LYU Shengxiang. Study on the Influencing Factors of Gastric Cancer Based on Opportunistic Screening of Upper Gastrointestinal Cancer in Coastal Area of Northern Jiangsu [J]. Chinese General Practice, 2024, 27(09): 1042-1047.
[9]	GAO Rongjian, WU Haili, BI Jianhong, KANG Kai, GUO Xing, LIU Juan, LI Xiaoli, MENG Cunying. Related Factors of Pathological Upgrading in Gastric Mucosal Lesions after Endoscopic Submucosal Dissection [J]. Chinese General Practice, 2023, 26(26): 3325-3329.
[10]	CHEN Ruimin, LIU Fang, TAN Hong, HAN Shufang, CHEN Yingjian, SU Congcong. Effects of Dapagliflozin on the Expression of MicroRNA-423-5p and Cardiac Function in Patients with Type 2 Diabetes Mellitus and Chronic Heart Failure [J]. Chinese General Practice, 2023, 26(14): 1733-1738.
[11]	MIAO Xueyi, DING Lingyu, LU Jinling, HU Jieman, ZHU Hanfei, CHEN Li, XU Xinyi, XU Qin. Preoperative Frailty and Postoperative Adverse Outcomes among Elderly Patients with Gastric Cancer [J]. Chinese General Practice, 2023, 26(08): 980-988.
[12]	DING Lingyu, JIANG Xiaoman, MIAO Xueyi, CHEN Li, ZHU Hanfei, LU Jinling, HU Jieman, XU Xinyi, XU Qin. Perceived Influencing Factors of Preoperative Frailty among Elderly Patients with Gastric Cancer from the Perspective of Health Ecology: a Qualitative Study [J]. Chinese General Practice, 2023, 26(08): 972-979.
[13]	WU Fanying, LYU Wu, DU Kun, ZHOU Jingfan, HUANG Guolin, FENG Jie. Cancer Incidence Trend in Chinese Longevity Town Cenxi City from 2016 to 2020 [J]. Chinese General Practice, 2022, 25(32): 4079-4084.
[14]	Ziqiang HONG, Dacheng JIN, Xiangdou BAI, Baiqiang CUI, Yunjiu GOU. Recent Advances in the Diagnosis and Management of Multiple Primary Lung Cancer [J]. Chinese General Practice, 2022, 25(27): 3435-3442.
[15]	Like ZHANG, Lei MA, Fangyu SHI, Quanxiao XU. Expression of Programmed Death Ligand 1 and Density of CD₈⁺ Tumor-infiltrating T-lymphocytes in Gastric Cancer Tissues and Their Relationship with Clinicopathological Characteristics and Prognosis of Patients with Gastric Cancer [J]. Chinese General Practice, 2022, 25(18): 2262-2267.