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.	董令儀, 張輝, 葉穎江, 等. MicroRNA在結直腸癌中的研究進展. 中華外科雜志, 2010, 48(17): 1345-1347.
4.	Mohr AM, Mott JL. Overview of microRNA biology. Semin Liver Dis, 2015, 35(1): 3-11.
5.	劉麗. hTERT、miR-29c、miR-124、miR-135a 和 miR-148a 與胃癌的相關性研究. 南寧: 廣西醫科大學, 2016.
6.	林夢娟, 余保平. MiR-20a在胃癌中的作用及其診斷價值探討. 胃腸病學, 2017, 22(8): 506-509.
7.	張姣. Hsa-miR-29c 在食管鱗狀細胞癌中表達的臨床意義及功能研究. 南京: 東南大學, 2015.
8.	束翌俊. Hsa-miR-29c調控人膽囊癌細胞增殖轉移的機制研究. 上海: 上海交通大學, 2015.
9.	王濤. 第八版AJCC胃癌TNM分期對胃癌患者預后評價的有效性: 第七和第八版之間的比較研究. 沈陽: 中國醫科大學, 2018.
10.	張淦梅. 腫瘤病理診斷中特殊染色聯合免疫組化技術的應用效果及檢測陽性率評價. 臨床檢驗雜志 (電子版), 2019, 8(4): 262-263.
11.	肖本杰, 高麗, 耿冠男. 丁苯酞誘導缺氧條件下NDUFA4L2蛋白的高表達并參與腦保護的機制. 實用老年醫學, 2019, 33(10): 954-957.
12.	孫偉, 曹祥龍. 腹腔鏡輔助全胃切除術在不同年齡段進展期胃癌的對比研究. 中華普外科手術學雜志 (電子版), 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.	楊夢迪, 王學紅, 張梅. 表觀遺傳學在胃癌中的研究進展. 癌癥進展, 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, Magalh?es 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, 謝暉, 趙亞萍. hsa-miR-29c 生物信息學特征及其研究進展. 臨床檢驗雜志 (電子版), 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, Magalh?es 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, 王麗, 劉偉, 等. BMSC細胞外基質對脂肪間充質干細胞生物學活性的影響. 中華老年口腔醫學雜志, 2020, 18(2): 97-102.
26.	趙一朗, 劉滔, 楊惠林, 等. 細胞外基質增強人臍帶干細胞的抗氧化能力. 中國組織工程研究, 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, 黃凌霄, 陳聰, 等. 基質金屬蛋白酶在子宮內膜異位癥患者中的表達水平及在盆腔粘連中的作用. 中國婦幼保健, 2020, 35(8): 1390-1392.
29.	鄭熙, 余惠珍, 高潔, 等. TK-1和TIMP-1過表達對大鼠心肌梗死后心室重塑的影響. 中山大學學報 (醫學科學版), 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.	欒智華, 任晉宏, 薛慧清, 等. 黃芪糖蛋白對肺纖維化小鼠肺組織中α-SMA表達的影響. 中華中醫藥學刊, 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.	陳點點, 馮林春, 葉蕊, 等. miR-29b 通過靶向 PI3K/Akt 信號通路降低胃癌細胞對順鉑的耐受性. 中國醫學科學院學報, 2015, 37(5): 514-519.

1. 徐惠綿, 王鑫. 我國胃癌診治臨床研究現狀與展望. 中華胃腸外科雜志, 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. 董令儀, 張輝, 葉穎江, 等. MicroRNA在結直腸癌中的研究進展. 中華外科雜志, 2010, 48(17): 1345-1347.
4. Mohr AM, Mott JL. Overview of microRNA biology. Semin Liver Dis, 2015, 35(1): 3-11.
5. 劉麗. hTERT、miR-29c、miR-124、miR-135a 和 miR-148a 與胃癌的相關性研究. 南寧: 廣西醫科大學, 2016.
6. 林夢娟, 余保平. MiR-20a在胃癌中的作用及其診斷價值探討. 胃腸病學, 2017, 22(8): 506-509.
7. 張姣. Hsa-miR-29c 在食管鱗狀細胞癌中表達的臨床意義及功能研究. 南京: 東南大學, 2015.
8. 束翌俊. Hsa-miR-29c調控人膽囊癌細胞增殖轉移的機制研究. 上海: 上海交通大學, 2015.
9. 王濤. 第八版AJCC胃癌TNM分期對胃癌患者預后評價的有效性: 第七和第八版之間的比較研究. 沈陽: 中國醫科大學, 2018.
10. 張淦梅. 腫瘤病理診斷中特殊染色聯合免疫組化技術的應用效果及檢測陽性率評價. 臨床檢驗雜志 (電子版), 2019, 8(4): 262-263.
11. 肖本杰, 高麗, 耿冠男. 丁苯酞誘導缺氧條件下NDUFA4L2蛋白的高表達并參與腦保護的機制. 實用老年醫學, 2019, 33(10): 954-957.
12. 孫偉, 曹祥龍. 腹腔鏡輔助全胃切除術在不同年齡段進展期胃癌的對比研究. 中華普外科手術學雜志 (電子版), 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. 楊夢迪, 王學紅, 張梅. 表觀遺傳學在胃癌中的研究進展. 癌癥進展, 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, Magalh?es 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, 謝暉, 趙亞萍. hsa-miR-29c 生物信息學特征及其研究進展. 臨床檢驗雜志 (電子版), 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, Magalh?es 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, 王麗, 劉偉, 等. BMSC細胞外基質對脂肪間充質干細胞生物學活性的影響. 中華老年口腔醫學雜志, 2020, 18(2): 97-102.
26. 趙一朗, 劉滔, 楊惠林, 等. 細胞外基質增強人臍帶干細胞的抗氧化能力. 中國組織工程研究, 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, 黃凌霄, 陳聰, 等. 基質金屬蛋白酶在子宮內膜異位癥患者中的表達水平及在盆腔粘連中的作用. 中國婦幼保健, 2020, 35(8): 1390-1392.
29. 鄭熙, 余惠珍, 高潔, 等. TK-1和TIMP-1過表達對大鼠心肌梗死后心室重塑的影響. 中山大學學報 (醫學科學版), 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. 欒智華, 任晉宏, 薛慧清, 等. 黃芪糖蛋白對肺纖維化小鼠肺組織中α-SMA表達的影響. 中華中醫藥學刊, 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. 陳點點, 馮林春, 葉蕊, 等. miR-29b 通過靶向 PI3K/Akt 信號通路降低胃癌細胞對順鉑的耐受性. 中國醫學科學院學報, 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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