Value and mechanism of miR-429 in clinical prognosis of patients with pancreatic ductal adenocarcinoma

doi:10.3877/cma.j.issn.2095-3232.2021.06.020

Abstract

Abstract:

Objective

To evaluate the prognostic value and mechanism of miR-429 in patients with pancreatic ductal adenocarcinoma (PDAC).

Methods

Clinicopathological data of 95 PDAC patients admitted to Xuyi People's Hospital of Jiangsu province from June 2015 to August 2019 were retrospectively analyzed. The informed consents of all patients were obtained and the local ethical committee approval was received. Among them, 60 patients were male and 35 female, aged from 32 to 76 years, with a median age of 61 years. The expression level of miR-429 was detected by fluorescent quantitative RT-PCR. The relationship between miR-429 expression and survival and prognosis of the patients was analyzed. Human pancreatic cancer cell lines Bxpc-3 and Panc-1 were selected for cell experiment. The cell proliferation and migration capability was determined by MTT assay and Transwell chamber test. The expression levels of E-cadherin, N-cadherin and vimentin related to epithelial-mesenchymal transition (EMT) were detected by immunofluorescent staining. The relative expression level of miR-429 between two groups was compared by t test. The relationship between miR-429 expression and clinicopathological features of PDAC patients was analyzed by Chi-square test. Survival analysis was performed with Kaplan-Meier method and Log-rank test.

Results

The average relative expression level of miR-429 in tumor tissues of PDAC patients was 1.02±0.43, significantly lower than 2.35±0.27 in the adjacent normal tissues (t=-1.732, P<0.05). The expression level of miR-429 was correlated with TNM staging and tumor vascular invasion (χ²=3.877, 2.584; P<0.05). The overall survival and disease-free survival rates of PDAC patients with low expression of miR-429 were significantly decreased (χ²=2.874, 3.106; P<0.05). MTT assay revealed that miR-429 overexpression significantly inhibited the proliferation of Bxpc-3 and Panc-1 pancreatic cancer cells, whereas down-regulating miR-429 expression promoted cell proliferation. Up-regulation of miR-429 expression significantly inhibited the invasion and migration of Bxpc-3 and Panc-1 cells according to Transwell chamber test. The expression level of E-cadherin was up-regulated, whereas those of N-cadherin and vimentin were down-regulated in the tissues with low expression of miR-429 according to immunofluorescent staining.

Conclusions

miR-429 is lowly expressed in the PDAC tissues, which is associated with poor prognosis. miR-429 plays an anti-tumor role in PDAC patients by regulating the EMT process.

Key words: Pancreatic neoplasms, MicroRNAs, Neoplasm invasiveness, Neoplasm metastasis

Qian Zhu, Yiran Chen, Chao Shi, Jingyao Shen, Liang Xu, Jie Ying, Liping Hu. Value and mechanism of miR-429 in clinical prognosis of patients with pancreatic ductal adenocarcinoma[J]. Chinese Journal of Hepatic Surgery(Electronic Edition), 2021, 10(06): 629-635.

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References 28

[1]	Kaissis G, Braren R. Pancreatic cancer detection and characterization-state of the art cross-sectional imaging and imaging data analysis[J]. Transl Gastroenterol Hepatol, 2019(4):35.
[2]	Scheufele F, Hartmann D, Friess H. Treatment of pancreatic cancer-neoadjuvant treatment in borderline resectable/locally advanced pancreatic cancer[J]. Transl Gastroenterol Hepatol, 2019(4):32.
[3]	Furuse J. Treatments for pancreatic cancer with oligometastasis[J]. Gan To Kagaku Ryoho, 2017, 44(10):827-830.
[4]	Liang H, Yu T, Han Y, et al. LncRNA PTAR promotes EMT and invasion-metastasis in serous ovarian cancer by competitively binding miR-101-3p to regulate ZEB1 expression[J]. Mol Cancer, 2018, 17(1):119.
[5]	Ding XM. MicroRNAs: regulators of cancer metastasis and epithelial-mesenchymal transition (EMT)[J]. Chin J Cancer, 2014, 33(3):140-147.
[6]	Chen L, Gibbons DL, Goswami S, et al. Metastasis is regulated via microRNA-200/ZEB1 axis control of tumour cell PD-L1 expression and intratumoral immunosuppression[J]. Nat Commun, 2014(5): 5241.
[7]	Chen J, Wang L, Matyunina LV, et al. Overexpression of miR-429 induces mesenchymal-to-epithelial transition (MET) in metastatic ovarian cancer cells[J]. Gynecol Oncol, 2011, 121(1):200-205.
[8]	Kleeff J, Korc M, Apte M, et al. Pancreatic cancer[J]. Nat Rev Dis Primers, 2016(2):16022.
[9]	Velez-Serrano JF, Velez-Serrano D, Hernandez-Barrera V, et al. Prediction of in-hospital mortality after pancreatic resection in pancreatic cancer patients: a boosting approach via a population-based study using health administrative data[J]. PLoS One, 2017, 12(6):e0178757.
[10]	Miyazaki M, Yoshitomi H, Takano S, et al. Combined hepatic arterial resection in pancreatic resections for locally advanced pancreatic cancer[J]. Langenbecks Arch Surg, 2017, 402(3):447-456.
[11]	Brooks J, Fleischmann-Mundt B, Woller N, et al. Perioperative, spatiotemporally coordinated activation of T and NK cells prevents recurrence of pancreatic cancer[J]. Cancer Res, 2018, 78(2):475-488.
[12]	Ambe CM, Nguyen P, Centeno BA, et al. Multimodality management of "borderline besectable" pancreatic neuroendocrine tumors: report of a single-institution experience[J]. Cancer Control, 2017, 24(5): 1073274817729076.
[13]	Shi H, Li H, Zhen T, et al. hsa_circ_001653 implicates in the development of pancreatic ductal adenocarcinoma by regulating microRNA-377-mediated HOXC6 axis[J]. Mol Ther Nucleic Acids, 2020(20):252-264.
[14]	Oto J, Navarro S, Larsen AC, et al. MicroRNAs and neutrophil activation markers predict venous thrombosis in pancreatic ductal adenocarcinoma and distal extrahepatic cholangiocarcinoma[J]. Int J Mol Sci, 2020, 21(3): 840.
[15]	Fesler A, Ju J. Development of microRNA-based therapy for pancreatic cancer[J]. J Pancreatol, 2019, 2(4):147-151.
[16]	Wei H, Hu J, Pu J, et al. Long noncoding RNA HAGLROS promotes cell proliferation, inhibits apoptosis and enhances autophagy via regulating miR-5095/ATG12 axis in hepatocellular carcinoma cells[J]. Int Immunopharmacol, 2019(73):72-80.
[17]	Qiu M, Li T, Wang B, et al. miR-146a-5p regulated cell proliferation and apoptosis by targeting SMAD3 and SMAD4[J]. Protein Pept Lett, 2020, 27(5):411-418.
[18]	Chen HS, Lu AQ, Yang PY, et al. MicroRNA-28-5p regulates glioma cell proliferation, invasion and migration by targeting SphK1[J]. Eur Rev Med Pharmacol Sci, 2019, 23(15):6621-6628.
[19]	Xiong Y, Wang Y, Wang L, et al. MicroRNA-30b targets snail to impede epithelial-mesenchymal transition in pancreatic cancer stem cells[J]. J Cancer, 2018, 9(12):2147-2159.
[20]	Peng L, Liu Z, Xiao J, et al. MicroRNA-148a suppresses epithelial-mesenchymal transition and invasion of pancreatic cancer cells by targeting Wnt10b and inhibiting the Wnt/beta-catenin signaling pathway[J]. Oncol Rep, 2017, 38(1):301-308.
[21]	Stroese AJ, Ullerich H, Koehler G, et al. Circulating microRNA-99 family as liquid biopsy marker in pancreatic adenocarcinoma[J]. J Cancer Res Clin Oncol, 2018, 144(12):2377-2390.
[22]	Su Z, Jiang G, Chen J, et al. MicroRNA-429 inhibits cancer cell proliferation and migration by targeting AKT1 in renal cell carcinoma[J]. Mol Clin Oncol, 2020, 12(1):75-80.
[23]	Liu D, Xia P, Diao D, et al. MiRNA-429 suppresses the growth of gastric cancer cells in vitro[J]. J Biomed Res, 2012, 26(5):389-393.
[24]	Mo JS, Han SH, Yun KJ, et al. MicroRNA 429 regulates the expression of CHMP5 in the inflammatory colitis and colorectal cancer cells[J]. Inflamm Res, 2018, 67(11/12):985-996.
[25]	Yin C, Lin X, Wang Y, et al. FAM83D promotes epithelial-mesenchymal transition, invasion and cisplatin resistance through regulating the AKT/mTOR pathway in non-small-cell lung cancer[J]. Cell Oncol, 2020, 43(3):395-407.
[26]	Saberianpour S, Rezaie Nezhad Zamani A, Karimi A, et al. Hollow alginate-poly-L-lysine-alginate microspheres promoted an epithelial-mesenchymal transition in human colon adenocarcinoma cells[J]. Adv Pharm Bull, 2020, 10(1):141-145.
[27]	Lin L, Li Y, Liu M, et al. The Interleukin-33/ST2 axis promotes glioma mesenchymal transition, stemness and TMZ resistance via JNK activation[J]. Aging, 2020, 12(2):1685-1703.
[28]	Lamouille S, Xu J, Derynck R. Molecular mechanisms of epithelial-mesenchymal transition[J]. Nat Rev Mol Cell Biol, 2014, 15(3):178-196.

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