Effects of miR-451a on proliferation and apoptosis of human pancreatic cancer BxPc3 cells and its molecular mechanisms_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

 LIU Shaopeng , LIU Haichao , BAI Minghui

The Second Department of Hepatobiliary, Pancreatic, Splenic and Hernia Surgery, Luoyang Central Hospital Affiliated to Zhengzhou University, Luoyang, Henan 471000, P. R. China;

Corresponding?author：

LIU Shaopeng, Email: 1281733563@qq.com

Keywords：

pancreatic cancer; BxPc3 cells; miR-451a; PI3K/AKT signaling pathway; proliferation; apoptosis

DOI：

10.7507/1007-9424.202002037

Video：

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Objective To analyze the effects of miR-451a on the proliferation and apoptosis of human pancreatic cancer BxPc3 cells, and to explore its molecular mechanisms.Methods The liposome transfection mimics of miR-451a were established in the BxPc3 cells, which were used as the research objects, and different concentrations (25, 50, 100 and 200 μmol/L) of miR-451a and blank control group were set up respectively. The expression of miR-451a mRNA in the BxPc3 cells after the transfection was detected by the qRT-PCR method. The effects of miR-451a at different concentrations on the proliferation, cell clone number, cell cycle and apoptosis, and the expressions of the macrophage migration inhibitory factor (MIF), calcium binding protein 39 (CAB39), phosphorylated phosphatidylinositol-3-kinase (p-PI3K) and phosphorylated protein kinase B (p-AKT) proteins in the BxPc3 cells were detected by the MTT assay, plate cloning assay, flow cytometry, and Western blot, respectively.Results The expressions of miR-451a mRNA in the transfected BxPc3 cells were significantly higher than in the blank control BxPc3 cells (P<0.050). The miR-451a could inhibit the proliferation of BxPc3 cells in a time- and concentration-dependent manner significantly (P<0.050), block the differentiation of BxPc3 cells in the G0/G1 phase, and induce the apoptosis with a concentration-dependent manner (P<0.050). The expressions of MIF, CAB39, p-PI3K, and p-AKT proteins in the BxPc3 cells were down-regulated with a concentration-dependent manner (P<0.050).Conclusion From results of this study, miR-451a could inhibit proliferation and induce apoptosis of BxPc3 cells in a concentration-dependent manner, and its mechanisms might be related to inhibition of PI3K/AKT signaling pathway.

Citation： LIU Shaopeng, LIU Haichao, BAI Minghui. Effects of miR-451a on proliferation and apoptosis of human pancreatic cancer BxPc3 cells and its molecular mechanisms. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2020, 27(10): 1231-1235. doi: 10.7507/1007-9424.202002037 Copy

1.	劉夢奇, 吉順榮, 徐曉武, 等. 2019 年胰腺癌研究及診療新進展. 中國癌癥雜志, 2020, 30(1): 1-10.
2.	王琛, 樊勇, 夏博偉. 微創時代下胰腺癌診療進展. 中華腔鏡外科雜志(電子版), 2019, 12(5): 311-316.
3.	Furuse J, Shibahara J, Sugiyama M. Development of chemotherapy and significance of conversion surgery after chemotherapy in unresectable pancreatic cancer. J Hepatobiliary Pancreat Sci, 2018, 25(5): 261-268.
4.	Bacalbasa N, Balescu I, Vilcu M, <italic>et al</italic>. Pancreatoduodenectomy after neoadjuvant chemotherapy for locally advanced pancreatic cancer in the presence of an aberrant right hepatic artery. In Vivo, 2020, 34(1): 401-406.
5.	Tsujimoto A, Sudo K, Nakamura K, <italic>et al</italic>. Gemcitabine plus nab-paclitaxel for locally advanced or borderline resectable pancreatic cancer. Sci Rep, 2019, 9(1): 16187.
6.	孟慶榆, 劉淑杰, 代春梅, 等. MicroRNA-18a 對乳腺癌細胞 MCF-7/PTX 紫杉醇耐藥性的影響. 武漢大學學報(醫學版), 2020, 41(2): 225-230.
7.	Streleckiene G, Inciuraite R, Juzenas S, <italic>et al</italic>. miR-20b and miR-451a are involved in gastric carcinogenesis through the PI3K/AKT/mTOR signaling pathway: Data from gastric cancer patients, cell lines and Ins-Gas mouse model. Int J Mol Sci, 2020, 21(3): pii: E877.
8.	Xu K, Han B, Bai Y, <italic>et al</italic>. MiR-451a suppressing BAP31 can inhibit proliferation and increase apoptosis through inducing ER stress in colorectal cancer. Cell Death Dis, 2019, 10(3): 152.
9.	Wei GY, Hu M, Zhao L, <italic>et al</italic>. MiR-451a suppresses cell proliferation, metastasis and EMT <italic>via</italic> targeting YWHAZ in hepatocellular carcinoma. Eur Rev Med Pharmacol Sci, 2019, 23(12): 5158-5167.
10.	Nothnick WB, Swan K, Flyckt R, <italic>et al</italic>. Human endometriotic lesion expression of the miR-144-3p/miR-451a cluster, its correlation with markers of cell survival and origin of lesion content. Sci Rep, 2019, 9(1): 8823.
11.	葉辰, 原春輝. 胰腺癌免疫微環境及免疫治療的前景與展望. 中華外科雜志, 2019, 57(1): 10-15.
12.	戴紅梅, 洪夏飛, 龐海玉, 等. 主動脈旁淋巴結轉移對胰腺癌可切除性影響的研究進展. 中華外科雜志, 2019, 57(1): 68-71.
13.	Passardi A, Scarpi E, Neri E, <italic>et al</italic>. Chemoradiotherapy (gemox plus helical tomotherapy) for unresectable locally advanced pancreatic cancer: A phase Ⅱ Study. Cancers, 2019, 11(5): 663.
14.	Caruso R, Quijano Y, Ferri V, <italic>et al</italic>. Venous resection for locally advanced pancreatic cancer: time trend and outcome analysis of 65 consecutive resections at a high-volume center. Surg Technol Int, 2019, 35: 92-99.
15.	歐政林, 李宜雄, 紀連棟, 等. 胰腺癌新輔助治療的共識及爭議. 中華外科雜志, 2020, 58(2): 99-104.
16.	Grasso C, Jansen G, Giovannetti E. Drug resistance in pancreatic cancer: Impact of altered energy metabolism. Crit Rev Oncol Hematol, 2017, 114: 139-152.
17.	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.
18.	Li Y, Wang J, Dai X, <italic>et al</italic>. miR-451 regulates FoxO3 nuclear accumulation through Ywhaz in human colorectal cancer. Am J Transl Res, 2015, 7(12): 2775-2785.
19.	Su Z, Zhao J, Rong Z, <italic>et al</italic>. MiR-451, a potential prognostic biomarker and tumor suppressor for gastric cancer. Int J Clin Exp Pathol, 2015, 8(8): 9154-9160.
20.	Zang WQ, Yang X, Wang T, <italic>et al</italic>. MiR-451 inhibits proliferation of esophageal carcinoma cell line EC9706 by targeting CDKN2D and MAP3K1. World J Gastroenterol, 2015, 21(19): 5867-5876.
21.	Yin P, Peng R, Peng H, <italic>et al</italic>. MiR-451 suppresses cell proliferation and metastasis in A549 lung cancer cells. Mol Biotechnol, 2015, 57(1): 1-11.
22.	Gu X, Li JY, Guo J, <italic>et al</italic>. Influence of MiR-451 on drug resistances of paclitaxel-resistant breast cancer cell line. Med Sci Monit, 2015, 21: 3291-3297.
23.	常振宇, 張亞楠, 劉婕, 等. miR-451a 促進胰腺癌細胞對吉西他濱的敏感性. 生物技術通訊, 2019, 30(3): 308-314.
24.	O’Reilly C, Doroudian M, Mawhinney L, <italic>et al</italic>. Targeting MIF in cancer: therapeutic strategies, current developments, and future opportunities. Med Res Rev, 2016, 36(3): 440-460.
25.	Tian Y, Nan Y, Han L, <italic>et al</italic>. MicroRNA miR-451 downregulates the PI3K/AKT pathway through CAB39 in human glioma. Int J Oncol, 2012, 40(4): 1105-1112.
26.	羅燕, 陳志濤, 徐崇明, 等. VSL#3 通過 PI3K/Akt 信號通路調節潰瘍性結腸炎大鼠調節性T細胞表達. 華中科技大學學報(醫學版), 2019, 48(4): 411-416.
27.	Goto T, Fujiya M, Konishi H, <italic>et al</italic>. An elevated expression of serum exosomal microRNA-191, -21, -451a of pancreatic neoplasm is considered to be efficient diagnostic marker. BMC Cancer, 2018, 18(1): 116.

1. 劉夢奇, 吉順榮, 徐曉武, 等. 2019 年胰腺癌研究及診療新進展. 中國癌癥雜志, 2020, 30(1): 1-10.
2. 王琛, 樊勇, 夏博偉. 微創時代下胰腺癌診療進展. 中華腔鏡外科雜志(電子版), 2019, 12(5): 311-316.
3. Furuse J, Shibahara J, Sugiyama M. Development of chemotherapy and significance of conversion surgery after chemotherapy in unresectable pancreatic cancer. J Hepatobiliary Pancreat Sci, 2018, 25(5): 261-268.
4. Bacalbasa N, Balescu I, Vilcu M, <italic>et al</italic>. Pancreatoduodenectomy after neoadjuvant chemotherapy for locally advanced pancreatic cancer in the presence of an aberrant right hepatic artery. In Vivo, 2020, 34(1): 401-406.
5. Tsujimoto A, Sudo K, Nakamura K, <italic>et al</italic>. Gemcitabine plus nab-paclitaxel for locally advanced or borderline resectable pancreatic cancer. Sci Rep, 2019, 9(1): 16187.
6. 孟慶榆, 劉淑杰, 代春梅, 等. MicroRNA-18a 對乳腺癌細胞 MCF-7/PTX 紫杉醇耐藥性的影響. 武漢大學學報(醫學版), 2020, 41(2): 225-230.
7. Streleckiene G, Inciuraite R, Juzenas S, <italic>et al</italic>. miR-20b and miR-451a are involved in gastric carcinogenesis through the PI3K/AKT/mTOR signaling pathway: Data from gastric cancer patients, cell lines and Ins-Gas mouse model. Int J Mol Sci, 2020, 21(3): pii: E877.
8. Xu K, Han B, Bai Y, <italic>et al</italic>. MiR-451a suppressing BAP31 can inhibit proliferation and increase apoptosis through inducing ER stress in colorectal cancer. Cell Death Dis, 2019, 10(3): 152.
9. Wei GY, Hu M, Zhao L, <italic>et al</italic>. MiR-451a suppresses cell proliferation, metastasis and EMT <italic>via</italic> targeting YWHAZ in hepatocellular carcinoma. Eur Rev Med Pharmacol Sci, 2019, 23(12): 5158-5167.
10. Nothnick WB, Swan K, Flyckt R, <italic>et al</italic>. Human endometriotic lesion expression of the miR-144-3p/miR-451a cluster, its correlation with markers of cell survival and origin of lesion content. Sci Rep, 2019, 9(1): 8823.
11. 葉辰, 原春輝. 胰腺癌免疫微環境及免疫治療的前景與展望. 中華外科雜志, 2019, 57(1): 10-15.
12. 戴紅梅, 洪夏飛, 龐海玉, 等. 主動脈旁淋巴結轉移對胰腺癌可切除性影響的研究進展. 中華外科雜志, 2019, 57(1): 68-71.
13. Passardi A, Scarpi E, Neri E, <italic>et al</italic>. Chemoradiotherapy (gemox plus helical tomotherapy) for unresectable locally advanced pancreatic cancer: A phase Ⅱ Study. Cancers, 2019, 11(5): 663.
14. Caruso R, Quijano Y, Ferri V, <italic>et al</italic>. Venous resection for locally advanced pancreatic cancer: time trend and outcome analysis of 65 consecutive resections at a high-volume center. Surg Technol Int, 2019, 35: 92-99.
15. 歐政林, 李宜雄, 紀連棟, 等. 胰腺癌新輔助治療的共識及爭議. 中華外科雜志, 2020, 58(2): 99-104.
16. Grasso C, Jansen G, Giovannetti E. Drug resistance in pancreatic cancer: Impact of altered energy metabolism. Crit Rev Oncol Hematol, 2017, 114: 139-152.
17. 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.
18. Li Y, Wang J, Dai X, <italic>et al</italic>. miR-451 regulates FoxO3 nuclear accumulation through Ywhaz in human colorectal cancer. Am J Transl Res, 2015, 7(12): 2775-2785.
19. Su Z, Zhao J, Rong Z, <italic>et al</italic>. MiR-451, a potential prognostic biomarker and tumor suppressor for gastric cancer. Int J Clin Exp Pathol, 2015, 8(8): 9154-9160.
20. Zang WQ, Yang X, Wang T, <italic>et al</italic>. MiR-451 inhibits proliferation of esophageal carcinoma cell line EC9706 by targeting CDKN2D and MAP3K1. World J Gastroenterol, 2015, 21(19): 5867-5876.
21. Yin P, Peng R, Peng H, <italic>et al</italic>. MiR-451 suppresses cell proliferation and metastasis in A549 lung cancer cells. Mol Biotechnol, 2015, 57(1): 1-11.
22. Gu X, Li JY, Guo J, <italic>et al</italic>. Influence of MiR-451 on drug resistances of paclitaxel-resistant breast cancer cell line. Med Sci Monit, 2015, 21: 3291-3297.
23. 常振宇, 張亞楠, 劉婕, 等. miR-451a 促進胰腺癌細胞對吉西他濱的敏感性. 生物技術通訊, 2019, 30(3): 308-314.
24. O’Reilly C, Doroudian M, Mawhinney L, <italic>et al</italic>. Targeting MIF in cancer: therapeutic strategies, current developments, and future opportunities. Med Res Rev, 2016, 36(3): 440-460.
25. Tian Y, Nan Y, Han L, <italic>et al</italic>. MicroRNA miR-451 downregulates the PI3K/AKT pathway through CAB39 in human glioma. Int J Oncol, 2012, 40(4): 1105-1112.
26. 羅燕, 陳志濤, 徐崇明, 等. VSL#3 通過 PI3K/Akt 信號通路調節潰瘍性結腸炎大鼠調節性T細胞表達. 華中科技大學學報(醫學版), 2019, 48(4): 411-416.
27. Goto T, Fujiya M, Konishi H, <italic>et al</italic>. An elevated expression of serum exosomal microRNA-191, -21, -451a of pancreatic neoplasm is considered to be efficient diagnostic marker. BMC Cancer, 2018, 18(1): 116.

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Effects of miR-451a on proliferation and apoptosis of human pancreatic cancer BxPc3 cells and its molecular mechanisms

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