The Impact of MiRNA on the Molecular Mechanisms of Invasion and Metastasis in Pancreatic Cancer

Ketao Xiao; Dan Liu; Lin Wu; Lijin Zhao

doi:10.54097/bt64ec29

Authors

Ketao Xiao
Dan Liu
Lin Wu
Lijin Zhao

DOI:

https://doi.org/10.54097/bt64ec29

Keywords:

MiRNA, Pancreatic Cancer, Invasion and Metastasis

Abstract

Pancreatic cancer is a highly malignant tumor with a poor prognosis. Due to its highly invasive and metastatic characteristics, its five-year survival rate is extremely low. miRNA is a class of non-coding single-stranded RNA molecules with a length of about 20-24 nucleotides encoded by endogenous genes. A large number of studies have shown that miRNA is involved in various regulatory modes such as post-transcriptional gene expression regulation in the process of pancreatic cancer development, metastasis and invasion. MiRNA dysregulation is often observed in cancer, leading to disease progression. More and more studies have revealed specific changes in miRNA expression patterns and how they lead to the development of pancreatic cancer. This article summarizes the current research progress of miRNA in pancreatic cancer invasion and metastasis, providing a theoretical basis and new targets for the early diagnosis and treatment of pancreatic cancer.

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References

[1] RL S, AN G, A J. Cancer statistics, 2024[J/OL]. CA: a cancer journal for clinicians, 2024, 74(1)[2024-02-28]. DOI:10.3322/ caac.21820.

[2] WANG Y, YAN Q, FAN C, et. Overview and countermeasures of cancer burden in China[J/OL]. Science China. Life Sciences, 2023, 66(11): 2515-2526. DOI:10.1007/s11427-022-2240-6.

[3] W J, R Z, S Z, et al. Cancer statistics in Chinese older people, 2022: current burden, time trends, and comparisons with the US, Japan, and the Republic of Korea[J/OL]. Science China. Life sciences, 2023, 66(5)[2024-02-28].DOI:10.1007/s11427-022-2218-x.

[4] KLEEFF J, KORC M, APTE M, et al. Pancreatic cancer[J/OL]. Nature Reviews. Disease Primers, 2016, 2: 16022. DOI:10. 1038/ nrdp.2016.22.

[5] BRAVO-VÁZQUEZ L A, FRÍAS-REID N, RAMOS-DELGADO A G, et al. MicroRNAs and long non-coding RNAs in pancreatic cancer: From epigenetics to potential clinical applications[J/OL]. Translational Oncology, 2023, 27: 101579. DOI:10.1016/j.tranon.2022.101579.

[6] BARTEL D P. MicroRNAs: genomics, biogenesis, mechanism, and function[J/OL]. Cell, 2004, 116(2): 281-297. DOI:10. 1016/ s0092-8674(04)00045-5.

[7] ZHANG X, SAI B, WANG F, et al. Hypoxic BMSC-derived exosomal miRNAs promote metastasis of lung cancer cells via STAT3-induced EMT[J/OL]. Molecular Cancer, 2019, 18(1): 40. DOI:10.1186/s12943-019-0959-5.

[8] PAN G, LIU Y, SHANG L, et al. EMT-associated microRNAs and their roles in cancer stemness and drug resistance[J/OL]. Cancer Communications (London, England), 2021, 41(3): 199-217. DOI:10.1002/cac2.12138.

[9] GARZON R, FABBRI M, CIMMINO A, et al. MicroRNA expression and function in cancer[J/OL]. Trends in Molecular Medicine, 2006, 12(12): 580-587. DOI:10.1016/j. molmed. 2006. 10.006.

[10] HONG T H, PARK I Y. MicroRNA expression profiling of diagnostic needle aspirates from surgical pancreatic cancer specimens[J/OL]. Annals of Surgical Treatment and Research, 2014, 87(6): 290-297. DOI:10.4174/astr.2014.87.6.290.

[11] WANG J, CHEN J, SEN S. MicroRNA as Biomarkers and Diagnostics[J/OL]. Journal of Cellular Physiology, 2016, 231(1): 25-30. DOI:10.1002/jcp.25056.

[12] Y X, G N, E G, et al. Systematic analysis of microRNA expression of RNA extracted from fresh frozen and formalin-fixed paraffin-embedded samples[J/OL]. RNA (New York, N.Y.), 2007, 13(10)[2024-02-29]. https://pubmed.ncbi. nlm.nih.gov/17698639/. DOI:10.1261/rna.642907.

[13] HUANG J, LIU J, CHEN-XIAO K, et al. Advance in microRNA as a potential biomarker for early detection of pancreatic cancer[J/OL]. Biomarker Research, 2016, 4: 20. DOI:10.1186/s40364-016-0074-3.

[14] ALI SYEDA Z, LANGDEN S S S, MUNKHZUL C, et al. Regulatory Mechanism of MicroRNA Expression in Cancer[J/OL]. International Journal of Molecular Sciences, 2020, 21(5): 1723. DOI:10.3390/ijms21051723.

[15] HUANG X, ZHU X, YU Y, et al. Dissecting miRNA signature in colorectal cancer progression and metastasis[J/OL]. Cancer Letters, 2021, 501: 66-82. DOI:10.1016/j.canlet.2020.12.025.

[16] MicroRNA therapeutics: towards a new era for the management of cancer and other diseases - PubMed[EB/OL]. [2024-02-29]. https://pubmed.ncbi.nlm.nih.gov/28209991/.

[17] PALANICHAMY J K, RAO D S. miRNA dysregulation in cancer: towards a mechanistic understanding[J/OL]. Frontiers in Genetics, 2014, 5: 54. DOI:10.3389/fgene.2014.00054.

[18] FATHI M, GHAFOURI-FARD S, ABAK A, et al. Emerging roles of miRNAs in the development of pancreatic cancer [J/OL]. Biomedicine & Pharmacotherapy = Biomedecine & Pharmacotherapie, 2021, 141: 111914. DOI:10. 1016/ j.biopha. 2021. 111914.

[19] CANCER GENOME ATLAS RESEARCH NETWORK. ELECTRONIC ADDRESS: ANDREW_AGUIRRE @ DFCI.HARVARD.EDU, CANCER GENOME ATLAS RESEARCH NETWORK. Integrated Genomic Characterization of Pancreatic Ductal Adenocarcinoma [J/OL]. Cancer Cell, 2017, 32(2): 185-203.e13. DOI:10.1016/ j.ccell. 2017.07.007.

[20] LEE E J, GUSEV Y, JIANG J, et al. Expression profiling identifies microRNA signature in pancreatic cancer[J/OL]. International Journal of Cancer, 2007, 120(5): 1046-1054. DOI:10.1002/ijc.22394.

[21] Pancreatic cancer stroma: an update on therapeutic targeting strategies - PubMed[EB/OL]. [2024-03-05]. https://pubmed. ncbi.nlm.nih.gov/32393771/.

[22] PANG W, SU J, WANG Y, et al. Pancreatic cancer-secreted miR-155 implicates in the conversion from normal fibroblasts to cancer-associated fibroblasts[J/OL]. Cancer Science, 2015, 106(10): 1362-1369. DOI:10.1111/cas.12747.

[23] HAN Y, QIAN X, XU T, et al. Carcinoma-associated fibroblasts release microRNA-331-3p containing extracellular vesicles to exacerbate the development of pancreatic cancer via the SCARA5-FAK axis[J/OL]. Cancer Biology & Therapy, 2022, 23(1): 378-392. DOI:10.1080/15384047.2022.2041961.

[24] LIU T, CHEN Z, CHEN W, et al. Dysregulated miRNAs modulate tumor microenvironment associated signaling networks in pancreatic ductal adenocarcinoma[J/OL]. Precision Clinical Medicine, 2023, 6(1): pbad004. DOI: 10. 1093/ pcmedi/pbad004.

[25] KWON J J, NABINGER S C, VEGA Z, et al. Pathophysiological role of microRNA-29 in pancreatic cancer stroma[J/OL]. Scientific Reports, 2015, 5: 11450. DOI:10. 1038/ srep11450.

[26] BAKIR B, CHIARELLA A M, PITARRESI J R, et al. EMT, MET, Plasticity, and Tumor Metastasis[J/OL]. Trends in Cell Biology, 2020, 30(10): 764-776. DOI:10.1016/j. tcb. 2020. 07.003.

[27] EMT: 2016 - PubMed[EB/OL]. [2024-02-29]. https://pubmed. ncbi.nlm.nih.gov/27368099/.

[28] Chronic TGF-β exposure drives stabilized EMT, tumor stemness, and cancer drug resistance with vulnerability to bitopic mTOR inhibition - PubMed[EB/OL]. [2024-02-29]. https://pubmed.ncbi.nlm.nih.gov/30808819/.

[29] Hallmarks of cancer: the next generation - PubMed[EB/OL]. [2024-02-29]. https://pubmed.ncbi.nlm.nih.gov/21376230/.

[30] XU J, LIU S, YANG X, et al. Paracrine HGF promotes EMT and mediates the effects of PSC on chemoresistance by activating c-Met/PI3K/Akt signaling in pancreatic cancer in vitro[J/OL]. Life Sciences, 2020, 263: 118523. DOI:10.1016/j. lfs. 2020.118523.

[31] F C, S M, T G, et al. Early Dissemination of Circulating Tumor Cells: Biological and Clinical Insights[J/OL]. Frontiers in oncology, 2021, 11[2024-02-29]. https:// pubmed.ncbi. nlm. nih. gov/34026650/. DOI:10.3389/fonc.2021.672195.

[32] R L, M W, CR D, et al. Circulating tumour cells for early detection of clinically relevant cancer[J/OL]. Nature reviews. Clinical oncology, 2023, 20(7)[2024-02-29]. https://pubmed. ncbi. nlm.nih.gov/37268719/. DOI:10.1038/s41571-023-00781-y.

[33] MiR-361-3p regulates ERK1/2-induced EMT via DUSP2 mRNA degradation in pancreatic ductal adenocarcinoma - PubMed[EB/OL]. [2024-02-29]. https://pubmed. ncbi.nlm. nih. gov/ 30042387/.

[34] E K, S H, U B, et al. MicroRNA dysregulation in the tumor microenvironment influences the phenotype of pancreatic cancer[J/OL]. Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc, 2017, 30(8)[2024-02-29]. https://pubmed.ncbi. nlm.nih.gov/ 28548 126/. DOI:10.1038/modpathol.2017.35.

[35] Expression and Role of MicroRNAs from the miR-200 Family in the Tumor Formation and Metastatic Propensity of Pancreatic Cancer - PubMed[EB/OL]. [2024-02-29]. https:// pubmed. ncbi.nlm.nih.gov/31336236/.

[36] AKHMETKALIYEV A, ALIBRAHIM N, SHAFIEE D, et al. EMT/MET plasticity in cancer and Go-or-Grow decisions in quiescence: the two sides of the same coin?[J/OL]. Molecular Cancer, 2023, 22(1): 90. DOI:10.1186/s12943-023-01793-z.

[37] GREGORY P A, BERT A G, PATERSON E L, et al. The miR-200 family and miR-205 regulate epithelial to mesenchymal transition by targeting ZEB1 and SIP1[J/OL]. Nature Cell Biology, 2008, 10(5): 593-601. DOI:10.1038/ncb1722.

[38] Zinc-Dependent Regulation of ZEB1 and YAP1 Coactivation Promotes Epithelial-Mesenchymal Transition Plasticity and Metastasis in Pancreatic Cancer - PubMed[EB/OL]. [2024-02-29]. https://pubmed.ncbi.nlm.nih.gov/33421513/.

[39] ZEB1 turns into a transcriptional activator by interacting with YAP1 in aggressive cancer types - PubMed[EB/OL]. [2024-02-29]. https://pubmed.ncbi.nlm.nih.gov/26876920/.

[40] Hippo signaling regulates microprocessor and links cell-density-dependent miRNA biogenesis to cancer - PubMed[EB/OL]. [2024-02-29]. https://pubmed.ncbi. nlm.nih. gov/24581491/.

[41] A novel epigenetic CREB-miR-373 axis mediates ZIP4-induced pancreatic cancer growth - PubMed[EB/OL]. [2024-02-29]. https://pubmed.ncbi.nlm.nih.gov/23857777/.

[42] Effects of microRNA-183 on epithelial-mesenchymal transition, proliferation, migration, invasion and apoptosis in human pancreatic cancer SW1900 cells by targeting MTA1 - PubMed[EB/OL]. [2024-02-29]. https://pubmed.ncbi. nlm. nih. gov/28506766/.

[43] K P, A K, A T, et al. MicroRNA let-7 downregulates STAT3 phosphorylation in pancreatic cancer cells by increasing SOCS3 expression[J/OL]. Cancer letters, 2014, 347(1)[2024-02-29]. https://pubmed.ncbi.nlm.nih.gov/24491408/. DOI: 10. 1016/ j. canlet.2014.01.020.

[44] SHAO Z, CHEN X, QIU H, et al. CircNEK6 promotes the progression of pancreatic ductal adenocarcinoma through targeting miR-503/CCND1 axis[J/OL]. Translational Oncology, 2024, 39: 101810. DOI:10.1016/j. tranon.2023. 101 810.

[45] miR-24-3p Regulates Epithelial-Mesenchymal Transition and the Malignant Phenotype of Pancreatic Adenocarcinoma by Regulating ASF1B Expression - PubMed[EB/OL]. [2024-02-29]. https://pubmed.ncbi.nlm.nih.gov/36114946/.

[46] YAN H, BU P. Non-coding RNA in cancer[J/OL]. Essays in Biochemistry, 2021, 65(4): 625-639. DOI:10.1042/ EBC 2020 0032.

[47] ALESSIO E, BONADIO R S, BUSON L, et al. A Single Cell but Many Different Transcripts: A Journey into the World of Long Non-Coding RNAs[J/OL]. International Journal of Molecular Sciences, 2020, 21(1): 302. DOI:10.3390/ ijms210 10302.

[48] LncRNA SNHG12 contributes proliferation, invasion and epithelial-mesenchymal transition of pancreatic cancer cells by absorbing miRNA-320b - PubMed[EB/OL]. [2024-03-01]. https://pubmed.ncbi.nlm.nih.gov/32432698/.

[49] ZHANG Y, MA H, CHEN C. Long non‑coding RNA PCED1B‑AS1 promotes pancreatic ductal adenocarcinoma progression by regulating the miR‑411‑3p/HIF‑1α axis[J/OL]. Oncology Reports, 2021, 46(1): 134. DOI:10.3892/or. 2021. 8085.

[50] J X, W X, X Y, et al. LncRNA HCG11/miR-579-3p/MDM2 axis modulates malignant biological properties in pancreatic carcinoma via Notch/Hes1 signaling pathway[J/OL]. Aging, 2021, 13(12)[2024-03-01]. https://pubmed. ncbi.nlm.nih. gov/34230221/. DOI:10.18632/aging.203167.

[51] lncRNA THAP9-AS1 Promotes Pancreatic Ductal Adenocarcinoma Growth and Leads to a Poor Clinical Outcome via Sponging miR-484 and Interacting with YAP - PubMed[EB/OL]. [2024-03-01]. https://pubmed.ncbi. nlm.nih. gov/31831555/.

[52] Long noncoding RNA MIR31HG exhibits oncogenic property in pancreatic ductal adenocarcinoma and is negatively regulated by miR-193b - PubMed[EB/OL]. [2024-03-01]. https://pubmed.ncbi.nlm.nih.gov/26549028/.

[53] LIU P, YANG H, ZHANG J, et al. The lncRNA MALAT1 acts as a competing endogenous RNA to regulate KRAS expression by sponging miR-217 in pancreatic ductal adenocarcinoma [J/OL]. Scientific Reports, 2017, 7(1): 5186. DOI:10. 1038/ s41 598-017-05274-4.

[54] WU X B, FENG X, CHANG Q M, et al. Cross-talk among AFAP1-AS1, ACVR1 and microRNA-384 regulates the stemness of pancreatic cancer cells and tumorigenicity in nude mice[J/OL]. Journal of experimental & clinical cancer research: CR, 2019, 38(1): 107. DOI:10.1186/s13046-019-1051-0.

[55] Linc00511 acts as a competing endogenous RNA to regulate VEGFA expression through sponging hsa-miR-29b-3p in pancreatic ductal adenocarcinoma - PubMed[EB/OL]. [2024-03-01]. https://pubmed.ncbi.nlm.nih.gov/28984028/.

[56] JIANG Z, ZHOU J, DENG J, et al. Emerging roles of ferroptosis-related miRNAs in tumor metastasis[J/OL]. Cell Death Discovery, 2023, 9(1): 193. DOI:10.1038/s41420-023-01486-y.

[57] Exosome-mediated lncRNA SNHG11 regulates angiogenesis in pancreatic carcinoma through miR-324-3p/VEGFA axis - PubMed[EB/OL]. [2024-03-01]. https://pubmed. ncbi.nlm. nih. gov/34519129/.

[58] HIRSCHHORN T, STOCKWELL B R. The development of the concept of ferroptosis[J/OL]. Free Radical Biology & Medicine, 2019, 133: 130-143. DOI:10.1016/j. freeradbiomed. 2018.09.043.

[59] QI R, BAI Y, LI K, et al. Cancer-associated fibroblasts suppress ferroptosis and induce gemcitabine resistance in pancreatic cancer cells by secreting exosome-derived ACSL4-targeting miRNAs[J/OL]. Drug Resistance Updates: Reviews and Commentaries in Antimicrobial and Anticancer Chemotherapy, 2023, 68: 100960. DOI:10.1016/j. drup. 2023. 100960.

[60] Autophagy-Regulating microRNAs and Cancer - PubMed[EB/OL]. [2024-03-01]. https://pubmed. ncbi.nlm.nih. gov/28459042/.

[61] Autophagy: The Last Defense against Cellular Nutritional Stress - PubMed[EB/OL]. [2024-03-01]. https://pubmed. ncbi. nlm. nih.gov/30032222/.

[62] ZHAO Y, WANG Z, ZHANG W, et al. MicroRNAs play an essential role in autophagy regulation in various disease phenotypes[J/OL]. BioFactors (Oxford, England), 2019, 45(6): 844-856. DOI:10.1002/biof.1555.

[63] The Roles of Autophagy in Cancer - PubMed[EB/OL]. [2024-03-01]. https://pubmed.ncbi.nlm.nih.gov/30400561/.

[64] BARANGI S, HAYES A W, REITER R, et al. The therapeutic role of long non-coding RNAs in human diseases: A focus on the recent insights into autophagy[J/OL]. Pharmacological Research, 2019, 142: 22-29. DOI: 10.1016/j.phrs.2019.02.010.

[65] LIANG S, LI X, GAO C, et al. microRNA-based autophagy inhibition as targeted therapy in pancreatic cancer[J/OL]. Biomedicine & Pharmacotherapy = Biomedecine & Pharmacotherapie, 2020, 132: 110799. DOI:10. 1016/j.biopha. 2020. 110799.

[66] microRNA-7 impairs autophagy-derived pools of glucose to suppress pancreatic cancer progression - PubMed[EB/OL]. [2024-03-02]. https://pubmed.ncbi.nlm.nih.gov/28450156/.

[67] Downregulation of ULK1 by microRNA-372 inhibits the survival of human pancreatic adenocarcinoma cells - PubMed[EB/OL]. [2024-03-02]. https://pubmed.ncbi. nlm.nih. gov/28677209/.

[68] Therapeutic miR-506-3p Replacement in Pancreatic Carcinoma Leads to Multiple Effects including Autophagy, Apoptosis, Senescence, and Mitochondrial Alterations In Vitro and In Vivo - PubMed[EB/OL]. [2024-03-02]. https://pubmed. ncbi.nlm.nih.gov/35884996/.

[69] YANG Y, SUN Y, WANG H, et al. MicroRNA-221 induces autophagy through suppressing HDAC6 expression and promoting apoptosis in pancreatic cancer[J/OL]. Oncology Letters, 2018, 16(6): 7295-7301. DOI:10.3892/ol.2018.9513.

[70] YANG C, ZHANG J J, PENG Y P, et al. A Yin-Yang 1/miR-30a regulatory circuit modulates autophagy in pancreatic cancer cells[J/OL]. Journal of Translational Medicine, 2017, 15(1): 211. DOI:10.1186/s12967-017-1308-3.

[71] Exosomes: secreted vesicles and intercellular communications - PubMed[EB/OL]. [2024-03-02]. https://pubmed.ncbi. nlm. nih. gov/21876726/.

[72] VAN NIEL G, D’ANGELO G, RAPOSO G. Shedding light on the cell biology of extracellular vesicles[J/OL]. Nature Reviews. Molecular Cell Biology, 2018, 19(4): 213-228. DOI: 10. 1038/nrm.2017.125.

[73] Exosomal tumor microRNA modulates premetastatic organ cells - PubMed[EB/OL]. [2024-03-02]. https://pubmed. ncbi.nlm. nih.gov/23479506/.

[74] XIA X, ZHANG K, LUO G, et al. Downregulation of miR-301a-3p sensitizes pancreatic cancer cells to gemcitabine treatment via PTEN[J]. American Journal of Translational Research, 2017, 9(4): 1886-1895.

[75] ZACCARA S, RIES R J, JAFFREY S R. Reading, writing and erasing mRNA methylation[J/OL]. Nature Reviews. Molecular Cell Biology, 2019, 20(10): 608-624. DOI:10.1038/s41580-019-0168-5.

[76] Methylated nucleotides block 5’ terminus of HeLa cell messenger RNA - PubMed[EB/OL]. [2024-03-02]. https:// pubmed. ncbi.nlm.nih.gov/164293/.

[77] ROTTMAN F, SHATKIN A J, PERRY R P. Sequences containing methylated nucleotides at the 5’ termini of messenger RNAs: possible implications for processing[J/OL]. Cell, 1974, 3(3): 197-199. DOI:10.1016/0092-8674(74)90131-7.

[78] R D, K F, F R. Identification of methylated nucleosides in messenger RNA from Novikoff hepatoma cells[J/OL]. Proceedings of the National Academy of Sciences of the United States of America, 1974, 71(10) [2024-03-02]. https:// pubmed.ncbi.nlm.nih.gov/4372599/. DOI:10. 1073/pnas.71. 10. 3971.

[79] ADAMS J M, CORY S. Modified nucleosides and bizarre 5’-termini in mouse myeloma mRNA[J/OL]. Nature, 1975, 255(5503): 28-33. DOI:10.1038/255028a0.

[80] BOKAR J A, SHAMBAUGH M E, POLAYES D, et al. Purification and cDNA cloning of the AdoMet-binding subunit of the human mRNA (N6-adenosine)-methyltransferase[J]. RNA (New York, N.Y.), 1997, 3(11): 1233-1247.

[81] XIA T, WU X, CAO M, et al. The RNA m6A methyltransferase METTL3 promotes pancreatic cancer cell proliferation and invasion[J/OL]. Pathology, Research and Practice, 2019, 215(11): 152666. DOI:10.1016/j. prp.2019. 152666.

[82] ZHANG J, BAI R, LI M, et al. Excessive miR-25-3p maturation via N6-methyladenosine stimulated by cigarette smoke promotes pancreatic cancer progression[J/OL]. Nature Communications, 2019, 10(1): 1858. DOI:10.1038/s41467-019-09712-x.

[83] N(6)-methyladenosine-mediated miR-380-3p maturation and upregulation promotes cancer aggressiveness in pancreatic cancer - PubMed[EB/OL]. [2024-03-02]. https://pubmed.ncbi. nlm. nih.gov/35758158/.

[84] KONG F, LIU X, ZHOU Y, et al. Downregulation of METTL14 increases apoptosis and autophagy induced by cisplatin in pancreatic cancer cells[J/OL]. The International Journal of Biochemistry & Cell Biology, 2020, 122: 105731. DOI:10. 1016/j.biocel.2020.105731.