The expression of Hsa-miR-29c in gastric cancer and its clinical significance_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

SUN Sheng’an , BAI Minghui ,  HAN Baowei , WANG Yunshuai

Department of Gastrointestinal Surgery, Luoyang Central Hospital Affiliated to Zhengzhou University, Luoyang, Henan 471000, P. R. China;

Corresponding author：

HAN Baowei, Email: a18537919289@163.com

Keywords：

gastric cancer; Hsa-miR-29c; proliferation; prognosis

DOI：

10.7507/1007-9424.202005012

Video：

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Objective To analyze the expression of Hsa-miR-29c in gastric cancer and its mechanism of action, and to explore its relationship with clinicopathological characteristics and prognosis of gastric cancer patients.Methods Theoverexpression of Hsa-miR-29c in gastric cancer cell lines of MKN28 and MKN45 were established by lentivirus transfection (transfection group), and the control group of empty lentivirus (negative control group) was established. The expressions of Hsa-miR-29c in cells of the two groups after transfection were detected by real time polymerase chain reaction (qRT-PCR), and the proliferation and clonogenesis of cells in the two groups were detected by CCK-8 and plate cloning. The expression of extracellular matrix protein 1 (ECM1), type Ⅰ collagen (Col Ⅰ), smooth muscle actin(α-SMA), matrix metalloproteinase-2 (MMP-2), and tissue inhibitor of metalloproteinase-1 (TIMP-1) in the two groups were detected by Western blot. qRT-PCR and immunohistochemistry were used to detect the expression of Hsa-miR-29c in 70 gastric cancer tissues and adjacent tissues respectively, and then analyzed its relationship with the clinicopathological features and prognosis of gastric cancer.Results The stable expression of Hsa-miR-29c gastric cancer cell line was successfully constructed in this research, the expression of Hsa-miR-29c in the transfection group was significantly higher than that in the negative control group (P<0.05). The proliferation and clone forming ability of MKN28 and MKN45 cells in the transfection group were significantly lower than those in the negative control group (P<0.05). Compared with the negative control group, the expression of Col Ⅰ and TIMP-1 in MKN28 and MKN45 cells were increased after transfection, while the expression levels of ECM1, α-SMA, and MMP-2 were significantly decreased, with significant differences between the two groups (P<0.05). The expression level of Hsa-miR-29c in gastric cancer tissues was significantly lower than that of adjacent tissues (P<0.05), and the positive expression rate was not related to age, sex, and pathological type (P>0.05), but related to tumor size, TNM stage, tumor differentiation, and lymph node metastasis (P<0.05). The mean survival time (MST) of patients with negative expression of Hsa-miR-29c was significantly shorter than that of patients with positive expression (P=0.029).Conclusions Hsa-miR-29c is down expressed in gastric cancer, and is related to the clinical characteristics and prognosis of it. The overexpression of Hsa-miR-29c can inhibit the proliferation of gastric cancer cells, and the mechanism may be related to the inhibition of extracellular matrix (ECM) signaling pathway.

Citation： SUN Sheng’an, BAI Minghui, HAN Baowei, WANG Yunshuai. The expression of Hsa-miR-29c in gastric cancer and its clinical significance. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2021, 28(2): 200-207. doi: 10.7507/1007-9424.202005012 Copy

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2.	Wang X, Lu B, Dai C, et al. Caveolin-1 promotes chemoresistance of gastric cancer cells to cisplatin by activating WNT/β-catenin pathway. Front Oncol, 2020, 10: 46.
3.	董令仪, 张辉, 叶颖江, 等. MicroRNA在结直肠癌中的研究进展. 中华外科杂志, 2010, 48(17): 1345-1347.
4.	Mohr AM, Mott JL. Overview of microRNA biology. Semin Liver Dis, 2015, 35(1): 3-11.
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6.	林梦娟, 余保平. MiR-20a在胃癌中的作用及其诊断价值探讨. 胃肠病学, 2017, 22(8): 506-509.
7.	张姣. Hsa-miR-29c 在食管鳞状细胞癌中表达的临床意义及功能研究. 南京: 东南大学, 2015.
8.	束翌俊. Hsa-miR-29c调控人胆囊癌细胞增殖转移的机制研究. 上海: 上海交通大学, 2015.
9.	王涛. 第八版AJCC胃癌TNM分期对胃癌患者预后评价的有效性: 第七和第八版之间的比较研究. 沈阳: 中国医科大学, 2018.
10.	张淦梅. 肿瘤病理诊断中特殊染色联合免疫组化技术的应用效果及检测阳性率评价. 临床检验杂志 (电子版), 2019, 8(4): 262-263.
11.	肖本杰, 高丽, 耿冠男. 丁苯酞诱导缺氧条件下NDUFA4L2蛋白的高表达并参与脑保护的机制. 实用老年医学, 2019, 33(10): 954-957.
12.	孙伟, 曹祥龙. 腹腔镜辅助全胃切除术在不同年龄段进展期胃癌的对比研究. 中华普外科手术学杂志 (电子版), 2020, 14(1): 24-27.
13.	Taniguchi K, Ota M, Yamada T, et al. Staging of gastric cancer with the Clinical Stage Prediction score. World J Surg Oncol, 2019, 17(1): 47.
14.	Molaei F, Forghanifard MM, Fahim Y, et al. Molecular signaling in tumorigenesis of gastric cancer. Iran Biomed J, 2018, 22(4): 217-230.
15.	杨梦迪, 王学红, 张梅. 表观遗传学在胃癌中的研究进展. 癌症进展, 2019, 17(5): 503-506.
16.	Lin W, Miao Y, Meng X, et al. miRNA-765 mediates multidrug resistance via targeting BATF2 in gastric cancer cells. FEBS Open Bio, 2020, 10(6): 1021-1030.
17.	Abak A, Amini S, Sakhinia E, et al. MicroRNA-221: biogenesis, function and signatures in human cancers. Eur Rev Med Pharmacol Sci, 2018, 22(10): 3094-3117.
18.	Yang Q, Wu F, Mi Y, et al. Aberrant expression of miR-29b-3p influences heart development and cardiomyocyte proliferation by targeting NOTCH2. Cell Prolif, 2020, 53(3): e12764.
19.	Lopes CB, Magalhães LL, Teófilo CR, et al. Differential expression of hsa-miR-221, hsa-miR-21, hsa-miR-135b, and hsa-miR-29c suggests a field effect in oral cancer. BMC Cancer, 2018, 18(1): 721.
20.	Dostie J, Mourelatos Z, Yang M, et al. Numerous microRNPs in neuronal cells containing novel microRNAs. RNA, 2003, 9(2): 180-186.
21.	宋雷雷, 谢晖, 赵亚萍. hsa-miR-29c 生物信息学特征及其研究进展. 临床检验杂志 (电子版), 2012, 1(4): 211-215.
22.	Liu N, Tang LL, Sun Y, et al. MiR-29c suppresses invasion and metastasis by targeting TIAM1 in nasopharyngeal carcinoma. Cancer Lett, 2013, 329(2): 181-188.
23.	Zhao JJ, Lin J, Lwin T, et al. microRNA expression profile and identification of miR-29 as a prognostic marker and pathogenetic factor by targeting CDK6 in mantle cell lymphoma. Blood, 2010, 115(13): 2630-2639.
24.	Vidal AF, Cruz AMP, Magalhães L, et al. hsa-miR-29c and hsa-miR-135b differential expression as potential biomarker of gastric carcinogenesis. World J Gastroenterol, 2016, 22(6): 2060-2070.
25.	原芳芳, 王丽, 刘伟, 等. BMSC细胞外基质对脂肪间充质干细胞生物学活性的影响. 中华老年口腔医学杂志, 2020, 18(2): 97-102.
26.	赵一朗, 刘滔, 杨惠林, 等. 细胞外基质增强人脐带干细胞的抗氧化能力. 中国组织工程研究, 2020, 24(25): 3953-3958.
27.	Karoulias SZ, Beyens A, Balic Z, et al. A novel ADAMTS17 variant that causes Weill-Marchesani syndrome 4 alters fibrillin-1 and collagen type Ⅰ deposition in the extracellular matrix. Matrix Biol, 2020, 88: 1-18.
28.	郭敏, 黄凌霄, 陈聪, 等. 基质金属蛋白酶在子宫内膜异位症患者中的表达水平及在盆腔粘连中的作用. 中国妇幼保健, 2020, 35(8): 1390-1392.
29.	郑熙, 余惠珍, 高洁, 等. TK-1和TIMP-1过表达对大鼠心肌梗死后心室重塑的影响. 中山大学学报 (医学科学版), 2020, 41(3): 403-414.
30.	Fan W, Liu T, Chen W, et al. ECM1 prevents activation of transforming growth factor β, hepatic stellate cells, and fibrogenesis in mice. Gastroenterology, 2019, 157(5): 1352-1367.
31.	栾智华, 任晋宏, 薛慧清, 等. 黄芪糖蛋白对肺纤维化小鼠肺组织中α-SMA表达的影响. 中华中医药学刊, 2020, 38(6): 197-200, 274-276.
32.	Ni YJ, Lu J, Zhou HM. Propofol suppresses proliferation, migration and invasion of gastric cancer cells via regulating miR-29/MMP-2 axis. Eur Rev Med Pharmacol Sci, 2019, 23(23): 10177.
33.	Zhao X, Hou Y, Tuo Z, et al. Application values of miR-194 and miR-29 in the diagnosis and prognosis of gastric cancer. Exp Ther Med, 2018, 15(5): 4179-4184.
34.	Zhang H, Bai M, Deng T, et al. Cell-derived microvesicles mediate the delivery of miR-29a/c to suppress angiogenesis in gastric carcinoma. Cancer Lett, 2016, 375(2): 331-339.
35.	Wang D, Fan Z, Liu F, et al. Hsa-miR-21 and Hsa-miR-29 in tissue as potential diagnostic and prognostic biomarkers for gastric cancer. Cell Physiol Biochem, 2015, 37(4): 1454-1462.
36.	Cui H, Wang L, Gong P, et al. Deregulation between miR-29b/c and DNMT3A is associated with epigenetic silencing of the CDH1 gene, affecting cell migration and invasion in gastric cancer. PLoS One, 2015, 10(4): e0123926.
37.	Gong J, Li J, Wang Y, et al. Characterization of microRNA-29 family expression and investigation of their mechanistic roles in gastric cancer. Carcinogenesis, 2014, 35(2): 497-506.
38.	Wang Y, Liu C, Luo M, et al. Chemotherapy-induced miRNA-29c/Catenin-δ signaling suppresses metastasis in gastric cancer. Cancer Res, 2015, 75(7): 1332-1344.
39.	陈点点, 冯林春, 叶蕊, 等. miR-29b 通过靶向 PI3K/Akt 信号通路降低胃癌细胞对顺铂的耐受性. 中国医学科学院学报, 2015, 37(5): 514-519.

1. 徐惠绵, 王鑫. 我国胃癌诊治临床研究现状与展望. 中华胃肠外科杂志, 2020, 23(2): 109-114.
2. Wang X, Lu B, Dai C, et al. Caveolin-1 promotes chemoresistance of gastric cancer cells to cisplatin by activating WNT/β-catenin pathway. Front Oncol, 2020, 10: 46.
3. 董令仪, 张辉, 叶颖江, 等. MicroRNA在结直肠癌中的研究进展. 中华外科杂志, 2010, 48(17): 1345-1347.
4. Mohr AM, Mott JL. Overview of microRNA biology. Semin Liver Dis, 2015, 35(1): 3-11.
5. 刘丽. hTERT、miR-29c、miR-124、miR-135a 和 miR-148a 与胃癌的相关性研究. 南宁: 广西医科大学, 2016.
6. 林梦娟, 余保平. MiR-20a在胃癌中的作用及其诊断价值探讨. 胃肠病学, 2017, 22(8): 506-509.
7. 张姣. Hsa-miR-29c 在食管鳞状细胞癌中表达的临床意义及功能研究. 南京: 东南大学, 2015.
8. 束翌俊. Hsa-miR-29c调控人胆囊癌细胞增殖转移的机制研究. 上海: 上海交通大学, 2015.
9. 王涛. 第八版AJCC胃癌TNM分期对胃癌患者预后评价的有效性: 第七和第八版之间的比较研究. 沈阳: 中国医科大学, 2018.
10. 张淦梅. 肿瘤病理诊断中特殊染色联合免疫组化技术的应用效果及检测阳性率评价. 临床检验杂志 (电子版), 2019, 8(4): 262-263.
11. 肖本杰, 高丽, 耿冠男. 丁苯酞诱导缺氧条件下NDUFA4L2蛋白的高表达并参与脑保护的机制. 实用老年医学, 2019, 33(10): 954-957.
12. 孙伟, 曹祥龙. 腹腔镜辅助全胃切除术在不同年龄段进展期胃癌的对比研究. 中华普外科手术学杂志 (电子版), 2020, 14(1): 24-27.
13. Taniguchi K, Ota M, Yamada T, et al. Staging of gastric cancer with the Clinical Stage Prediction score. World J Surg Oncol, 2019, 17(1): 47.
14. Molaei F, Forghanifard MM, Fahim Y, et al. Molecular signaling in tumorigenesis of gastric cancer. Iran Biomed J, 2018, 22(4): 217-230.
15. 杨梦迪, 王学红, 张梅. 表观遗传学在胃癌中的研究进展. 癌症进展, 2019, 17(5): 503-506.
16. Lin W, Miao Y, Meng X, et al. miRNA-765 mediates multidrug resistance via targeting BATF2 in gastric cancer cells. FEBS Open Bio, 2020, 10(6): 1021-1030.
17. Abak A, Amini S, Sakhinia E, et al. MicroRNA-221: biogenesis, function and signatures in human cancers. Eur Rev Med Pharmacol Sci, 2018, 22(10): 3094-3117.
18. Yang Q, Wu F, Mi Y, et al. Aberrant expression of miR-29b-3p influences heart development and cardiomyocyte proliferation by targeting NOTCH2. Cell Prolif, 2020, 53(3): e12764.
19. Lopes CB, Magalhães LL, Teófilo CR, et al. Differential expression of hsa-miR-221, hsa-miR-21, hsa-miR-135b, and hsa-miR-29c suggests a field effect in oral cancer. BMC Cancer, 2018, 18(1): 721.
20. Dostie J, Mourelatos Z, Yang M, et al. Numerous microRNPs in neuronal cells containing novel microRNAs. RNA, 2003, 9(2): 180-186.
21. 宋雷雷, 谢晖, 赵亚萍. hsa-miR-29c 生物信息学特征及其研究进展. 临床检验杂志 (电子版), 2012, 1(4): 211-215.
22. Liu N, Tang LL, Sun Y, et al. MiR-29c suppresses invasion and metastasis by targeting TIAM1 in nasopharyngeal carcinoma. Cancer Lett, 2013, 329(2): 181-188.
23. Zhao JJ, Lin J, Lwin T, et al. microRNA expression profile and identification of miR-29 as a prognostic marker and pathogenetic factor by targeting CDK6 in mantle cell lymphoma. Blood, 2010, 115(13): 2630-2639.
24. Vidal AF, Cruz AMP, Magalhães L, et al. hsa-miR-29c and hsa-miR-135b differential expression as potential biomarker of gastric carcinogenesis. World J Gastroenterol, 2016, 22(6): 2060-2070.
25. 原芳芳, 王丽, 刘伟, 等. BMSC细胞外基质对脂肪间充质干细胞生物学活性的影响. 中华老年口腔医学杂志, 2020, 18(2): 97-102.
26. 赵一朗, 刘滔, 杨惠林, 等. 细胞外基质增强人脐带干细胞的抗氧化能力. 中国组织工程研究, 2020, 24(25): 3953-3958.
27. Karoulias SZ, Beyens A, Balic Z, et al. A novel ADAMTS17 variant that causes Weill-Marchesani syndrome 4 alters fibrillin-1 and collagen type Ⅰ deposition in the extracellular matrix. Matrix Biol, 2020, 88: 1-18.
28. 郭敏, 黄凌霄, 陈聪, 等. 基质金属蛋白酶在子宫内膜异位症患者中的表达水平及在盆腔粘连中的作用. 中国妇幼保健, 2020, 35(8): 1390-1392.
29. 郑熙, 余惠珍, 高洁, 等. TK-1和TIMP-1过表达对大鼠心肌梗死后心室重塑的影响. 中山大学学报 (医学科学版), 2020, 41(3): 403-414.
30. Fan W, Liu T, Chen W, et al. ECM1 prevents activation of transforming growth factor β, hepatic stellate cells, and fibrogenesis in mice. Gastroenterology, 2019, 157(5): 1352-1367.
31. 栾智华, 任晋宏, 薛慧清, 等. 黄芪糖蛋白对肺纤维化小鼠肺组织中α-SMA表达的影响. 中华中医药学刊, 2020, 38(6): 197-200, 274-276.
32. Ni YJ, Lu J, Zhou HM. Propofol suppresses proliferation, migration and invasion of gastric cancer cells via regulating miR-29/MMP-2 axis. Eur Rev Med Pharmacol Sci, 2019, 23(23): 10177.
33. Zhao X, Hou Y, Tuo Z, et al. Application values of miR-194 and miR-29 in the diagnosis and prognosis of gastric cancer. Exp Ther Med, 2018, 15(5): 4179-4184.
34. Zhang H, Bai M, Deng T, et al. Cell-derived microvesicles mediate the delivery of miR-29a/c to suppress angiogenesis in gastric carcinoma. Cancer Lett, 2016, 375(2): 331-339.
35. Wang D, Fan Z, Liu F, et al. Hsa-miR-21 and Hsa-miR-29 in tissue as potential diagnostic and prognostic biomarkers for gastric cancer. Cell Physiol Biochem, 2015, 37(4): 1454-1462.
36. Cui H, Wang L, Gong P, et al. Deregulation between miR-29b/c and DNMT3A is associated with epigenetic silencing of the CDH1 gene, affecting cell migration and invasion in gastric cancer. PLoS One, 2015, 10(4): e0123926.
37. Gong J, Li J, Wang Y, et al. Characterization of microRNA-29 family expression and investigation of their mechanistic roles in gastric cancer. Carcinogenesis, 2014, 35(2): 497-506.
38. Wang Y, Liu C, Luo M, et al. Chemotherapy-induced miRNA-29c/Catenin-δ signaling suppresses metastasis in gastric cancer. Cancer Res, 2015, 75(7): 1332-1344.
39. 陈点点, 冯林春, 叶蕊, 等. miR-29b 通过靶向 PI3K/Akt 信号通路降低胃癌细胞对顺铂的耐受性. 中国医学科学院学报, 2015, 37(5): 514-519.

CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

The expression of Hsa-miR-29c in gastric cancer and its clinical significance

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