Expression, clinical and biological significance of circulating miRNA-196a in patients withadvanced gastric cancer_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

LIU Wenneng ¹ , YANG Bairen ² , LI Dong ¹ , XIANG Lili ¹ ,  YANG Chuanhua ¹

1. West China School of Public Health, Sichuan University/Department of Gastrointestinal Surgery of West China Fourth Hospital, Sichuan University, Chengdu 610041, P. R. China;
2. Department of General Surgery, Yibin First People’s Hospital, Yibin, Sichuan 644000, P. R. China;

Corresponding?author：

YANG Chuanhua, Email: 249707720@qq.com

Keywords：

miRNA-196a; gastric cancer; invasiveness

DOI：

10.7507/1007-9424.202011033

Video：

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Objective To explore expression, clinical and biological significance of plasma miRNA-196a from patients with advanced gastric cancer.Methods Real time quantitative RT-PCR (qRT-PCR) method was used to detect the miRNA-196a levels in tissues and plasma from 75 gastric cancer patients and 35 benign gastric lesions controls. Then clinic pathological correlations of plasma miRNA-196a in 75 gastric cancer patients were analyzed. Twenty-five gastric cancer patients were randomized selected from 75 patients, to compare plasma miRNA-196a levels between preoperation and postoperation. Meanwhile, the effect of miRNA-196a on the invasion ability of gastric cancer MGC-803 cell line was observed in vitro.Results The levels of miRNA-196a in both plasma and tissues from 75 gastric cancer patients were significantly increased compared with 35 benign gastric lesions controls (P<0.000 1). Clinic pathological data of 75 gastric cancer patients showed that the expressions of miRNA-196a were significantly up-regulated in gastric cancer patients with serosal invasion (P<0.001), lymph node metastasis (P=0.004), distant metastasis (P<0.001) and late clinical stage (P<0.001). The expression of miRNA-196a in peripheral plasma of patients with gastric cancer was significantly down regulated after operation (P<0.000 1). In vitro, overexpression of miRNA-196a significantly increased the invasion ability of MGC-803 cells (P<0.05), whereas knockdown of endogenous miRNA-196a significantly inhibited the invasion ability of MGC-803 cells (P<0.05).Conclusions The expression of miRNA-196a is up-regulated not only in peripheral plasma of patients with gastric cancer, but also with the progression of gastric cancer (serosal invasion, lymph node metastasis and distant metastasis). The up-regulation of miRNA-196a expression in peripheral plasma is mainly due to the release of primary tumor tissue. miRNA-196a is expected to be a prognostic marker and a potential therapeutic target for advanced gastric cancer.

Citation： LIU Wenneng, YANG Bairen, LI Dong, XIANG Lili, YANG Chuanhua. Expression, clinical and biological significance of circulating miRNA-196a in patients withadvanced gastric cancer. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2021, 28(8): 1025-1030. doi: 10.7507/1007-9424.202011033 Copy

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2.	Nie RC, Yuan SQ, Chen S, et al. Bursectomy for advanced gastric cancer: an update meta-analysis. World J Surg Oncol, 2018, 16(1): 66.
3.	Yusefi AR, Bagheri Lankarani K, Bastani P, et al. Risk factors for gastric cancer: a systematic review. Asian Pac J Cancer Prev, 2018, 19(3): 591-603.
4.	Delgado-Guillena P, Morales-Alvarado V, Ramírez Salazar C, et al. Frequency and clinical characteristics of early gastric cancer in comparison to advanced gastric cancer in a health area of Spain. Gastroenterol Hepatol, 2020, 43(9): 506-514.
5.	Horiuchi Y, Hirasawa T, Ishizuka N, et al. Performance of a computer-aided diagnosis system in diagnosing early gastric cancer using magnifying endoscopy videos with narrow-band imaging (with videos). Gastrointest Endosc, 2020, 92(4): 856-865.
6.	Luo SS, Liao XW, Zhu XD. Genome-wide analysis to identify a novel microRNA signature that predicts survival in patients with stomach adenocarcinoma. J Cancer, 2019, 10(25): 6298-6313.
7.	de Nigris F. Epigenetic regulators: Polycomb-miRNA circuits in cancer. Biochim Biophys Acta, 2016, 1859(5): 697-704.
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9.	Ganju A, Khan S, Hafeez BB, et al. miRNA nanotherapeutics for cancer. Drug Discov Today, 2017, 22(2): 424-432.
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12.	Hemmat N, Mokhtarzadeh A, Aghazadeh M, et al. Role of microRNAs in epidermal growth factor receptor signaling pathway in cervical cancer. Mol Biol Rep, 2020, 47(6): 4553-4568.
13.	Tang S, Yu S, Cheng J, et al. The versatile roles and clinical implications of exosomal mRNAs and microRNAs in cancer. Int J Biol Markers, 2020, 35(2): 3-19.
14.	Donkers H, Bekkers R, Galaal K. Diagnostic value of microRNA panel in endometrial cancer: A systematic review. Oncotarget, 2020, 11(21): 2010-2023.
15.	Powrózek T, Porgador A, Ma?ecka-Massalska T. Detection, prediction, and prognosis: blood circulating microRNA as novel molecular markers of head and neck cancer patients. Expert Rev Mol Diagn, 2020, 20(1): 31-39.
16.	Terrinoni A, Calabrese C, Basso D, et al. The circulating miRNAs as diagnostic and prognostic markers. Clin Chem Lab Med, 2019, 57(7): 932-953.
17.	Chayeb V, Mahjoub S, Zitouni H, et al. Contribution of microRNA-149, microRNA-146a, and microRNA-196a2 SNPs in colorectal cancer risk and clinicopathological features in Tunisia. Gene, 2018, 666: 100-107.
18.	Pourdavoud P, Pakzad B, Mosallaei M, et al. MiR-196: emerging of a new potential therapeutic target and biomarker in colorectal cancer. Mol Biol Rep, 2020, 47(12): 9913-9920.
19.	Shahabi A, Naghili B, Ansarin K, et al. miR-140 and miR-196a as potential biomarkers in breast cancer patients. Asian Pac J Cancer Prev, 2020, 21(7): 1913-1918.
20.	Yu Q, Xu C, Yuan W, et al. Evaluation of plasma micrornas as diagnostic and prognostic biomarkers in pancreatic adenocarcinoma: miR-196a and miR-210 could be negative and positive prognostic markers, respectively. Biomed Res Int, 2017, 2017: 6495867.
21.	Liu Q, Bai W, Huang F, et al. Downregulation of microRNA-196a inhibits stem cell self-renewal ability and stemness in non-small-cell lung cancer through upregulating GPX3 expression. Int J Biochem Cell Biol, 2019, 115: 105571.
22.	Tsai MM, Wang CS, Tsai CY, et al. MicroRNA-196a/-196b promote cell metastasis via negative regulation of radixin in human gastric cancer. Cancer Lett, 2014, 351(2): 222-231.
23.	Chen TH, Lee C, Chiu CT, et al. Circulating microRNA-196a is an early gastric cancer biomarker. Oncotarget, 2017, 9(12): 10317-10323.
24.	Liu JY, Peng CW, Yang XJ, et al. The prognosis role of AJCC/UICC 8^th edition staging system in gastric cancer, a retrospective analysis. Am J Transl Res, 2018, 10(1): 292-303.
25.	Varkonyi-Gasic E, Hellens RP. Quantitative stem-loop RT-PCR for detection of microRNAs. Methods Mol Biol, 2011, 744: 145-157.
26.	Hurley J, Roberts D, Bond A, et al. Stem-loop RT-qPCR for microRNA expression profiling. Methods Mol Biol, 2012, 822: 33-52.
27.	杜亞瓊, 姜波健, 俞繼衛. miRNA在胃癌發生發展中的作用. 中國普外基礎與臨床雜志, 2016, 23(4): 499-502.

1. Tsukamoto T, Nakagawa M, Kiriyama Y, et al. Prevention of gastric cancer: eradication of Helicobacter Pylori and beyond. Int J Mol Sci, 2017, 18(8): 1699.
2. Nie RC, Yuan SQ, Chen S, et al. Bursectomy for advanced gastric cancer: an update meta-analysis. World J Surg Oncol, 2018, 16(1): 66.
3. Yusefi AR, Bagheri Lankarani K, Bastani P, et al. Risk factors for gastric cancer: a systematic review. Asian Pac J Cancer Prev, 2018, 19(3): 591-603.
4. Delgado-Guillena P, Morales-Alvarado V, Ramírez Salazar C, et al. Frequency and clinical characteristics of early gastric cancer in comparison to advanced gastric cancer in a health area of Spain. Gastroenterol Hepatol, 2020, 43(9): 506-514.
5. Horiuchi Y, Hirasawa T, Ishizuka N, et al. Performance of a computer-aided diagnosis system in diagnosing early gastric cancer using magnifying endoscopy videos with narrow-band imaging (with videos). Gastrointest Endosc, 2020, 92(4): 856-865.
6. Luo SS, Liao XW, Zhu XD. Genome-wide analysis to identify a novel microRNA signature that predicts survival in patients with stomach adenocarcinoma. J Cancer, 2019, 10(25): 6298-6313.
7. de Nigris F. Epigenetic regulators: Polycomb-miRNA circuits in cancer. Biochim Biophys Acta, 2016, 1859(5): 697-704.
8. Rupaimoole R, Calin GA, Lopez-Berestein G, et al. miRNA deregulation in cancer cells and the tumor microenvironment. Cancer Discov, 2016, 6(3): 235-246.
9. Ganju A, Khan S, Hafeez BB, et al. miRNA nanotherapeutics for cancer. Drug Discov Today, 2017, 22(2): 424-432.
10. Hao NB, He YF, Li XQ, et al. The role of miRNA and lncRNA in gastric cancer. Oncotarget, 2017, 8(46): 81572-81582.
11. Chen SC, Chen KT, Jou AF. Polydopamine-gold composite-based electrochemical biosensor using dual-amplification strategy for detecting pancreatic cancer-associated microRNA. Biosens Bioelectron, 2021, 173: 112815.
12. Hemmat N, Mokhtarzadeh A, Aghazadeh M, et al. Role of microRNAs in epidermal growth factor receptor signaling pathway in cervical cancer. Mol Biol Rep, 2020, 47(6): 4553-4568.
13. Tang S, Yu S, Cheng J, et al. The versatile roles and clinical implications of exosomal mRNAs and microRNAs in cancer. Int J Biol Markers, 2020, 35(2): 3-19.
14. Donkers H, Bekkers R, Galaal K. Diagnostic value of microRNA panel in endometrial cancer: A systematic review. Oncotarget, 2020, 11(21): 2010-2023.
15. Powrózek T, Porgador A, Ma?ecka-Massalska T. Detection, prediction, and prognosis: blood circulating microRNA as novel molecular markers of head and neck cancer patients. Expert Rev Mol Diagn, 2020, 20(1): 31-39.
16. Terrinoni A, Calabrese C, Basso D, et al. The circulating miRNAs as diagnostic and prognostic markers. Clin Chem Lab Med, 2019, 57(7): 932-953.
17. Chayeb V, Mahjoub S, Zitouni H, et al. Contribution of microRNA-149, microRNA-146a, and microRNA-196a2 SNPs in colorectal cancer risk and clinicopathological features in Tunisia. Gene, 2018, 666: 100-107.
18. Pourdavoud P, Pakzad B, Mosallaei M, et al. MiR-196: emerging of a new potential therapeutic target and biomarker in colorectal cancer. Mol Biol Rep, 2020, 47(12): 9913-9920.
19. Shahabi A, Naghili B, Ansarin K, et al. miR-140 and miR-196a as potential biomarkers in breast cancer patients. Asian Pac J Cancer Prev, 2020, 21(7): 1913-1918.
20. Yu Q, Xu C, Yuan W, et al. Evaluation of plasma micrornas as diagnostic and prognostic biomarkers in pancreatic adenocarcinoma: miR-196a and miR-210 could be negative and positive prognostic markers, respectively. Biomed Res Int, 2017, 2017: 6495867.
21. Liu Q, Bai W, Huang F, et al. Downregulation of microRNA-196a inhibits stem cell self-renewal ability and stemness in non-small-cell lung cancer through upregulating GPX3 expression. Int J Biochem Cell Biol, 2019, 115: 105571.
22. Tsai MM, Wang CS, Tsai CY, et al. MicroRNA-196a/-196b promote cell metastasis via negative regulation of radixin in human gastric cancer. Cancer Lett, 2014, 351(2): 222-231.
23. Chen TH, Lee C, Chiu CT, et al. Circulating microRNA-196a is an early gastric cancer biomarker. Oncotarget, 2017, 9(12): 10317-10323.
24. Liu JY, Peng CW, Yang XJ, et al. The prognosis role of AJCC/UICC 8^th edition staging system in gastric cancer, a retrospective analysis. Am J Transl Res, 2018, 10(1): 292-303.
25. Varkonyi-Gasic E, Hellens RP. Quantitative stem-loop RT-PCR for detection of microRNAs. Methods Mol Biol, 2011, 744: 145-157.
26. Hurley J, Roberts D, Bond A, et al. Stem-loop RT-qPCR for microRNA expression profiling. Methods Mol Biol, 2012, 822: 33-52.
27. 杜亞瓊, 姜波健, 俞繼衛. miRNA在胃癌發生發展中的作用. 中國普外基礎與臨床雜志, 2016, 23(4): 499-502.

CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Expression, clinical and biological significance of circulating miRNA-196a in patients withadvanced gastric cancer

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