miR-373 promotes invasion and metastasis of colorectal cancer cells via activating ERK/MAPK pathway.
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
02 Jan 2024
02 Jan 2024
Historique:
received:
25
08
2023
accepted:
09
12
2023
medline:
4
1
2024
pubmed:
4
1
2024
entrez:
3
1
2024
Statut:
epublish
Résumé
To explore the relationship between miR-373 and the occurrence and development of colorectal cancer. Additionally, it aims to predict the potential cellular signaling pathways and regulatory mechanisms in which miR-373 may be involved and provides a theoretical basis and experimental evidence for the clinical application of miR-373 as a potential biomarker, molecular target, and prognostic indicator in colorectal cancer. Real-time quantitative PCR is used to analyze the expression of miR-373 in human colorectal cancer cell lines and normal human colonic epithelial cells. Further validation of the differential expression of miR-373 in colorectal cancer cell lines is being performed. Biological functions such as cell proliferation, invasion and apoptosis are being detected by MTT, CCK-8, transwell, cell cycle analysis, and flow cytometry experiments to verify the changes in the biological behavior of colon cancer cells after overexpression and interference of miR-373 in SW-480 cells and to explore the effects of miR-373 on cell proliferation, invasion, and apoptosis in colon cancer cells. Proteomic analysis is being conducted on proteins extracted from miR-373 overexpressing SW480 cells, and mass spectrometry is used for protein identification. GO, KEGG, and enrichment analysis are being employed to analyze the significantly differentially expressed proteins. The expression levels of pathway-related proteins are being verified using Western blot. Overexpression of miR-373 increased the invasive and metastatic ability of SW-480 cells; knockdown of miR-373 decreased the invasive and metastatic ability of SW-480 cells. However, there was no statistically significant effect on cell proliferation and apoptosis in SW-480 cells. Proteomic analysis identified 78 differentially expressed proteins based on fold change (FC) > 1.2 and P < 0.05. Annotation of differentially changed proteins revealed that the MAPK signaling pathway, PI3K-Akt signaling pathway, and FAK signaling pathway may play crucial roles in the migration and invasion of colorectal cancer. Western blot analysis showed that overexpression of miR-373 significantly increased the levels of p-ERK1/2 in SW480 cells. miR-373 may activate the ERK/MAPK signaling pathway to promote the invasion and migration of colorectal cancer cells.
Identifiants
pubmed: 38167930
doi: 10.1038/s41598-023-49565-5
pii: 10.1038/s41598-023-49565-5
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
124Informations de copyright
© 2024. The Author(s).
Références
Sung, H. et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J. Clin. 71(3), 209–249. https://doi.org/10.3322/caac.21660 (2021).
doi: 10.3322/caac.21660
pubmed: 33538338
Tan Feifei, Xu. et al. Expression changes and clinical significance of miRNA-373 in endometrial cancer tissues. Shandong Med. J. 58(35), 3 (2018).
Yunhui, Qu. et al. The effect and mechanism of microRNA-373 on the proliferation and invasion ability of breast cancer cells. Chin. Med. J. 97(8), 5 (2017).
Qu, H. W., Jin, Y., Cui, Z. L. & Jin, X. B. MicroRNA-373-3p inhibits prostate cancer progression by targeting AKT1. Eur. Rev. Med. Pharmacol. Sci. 22(19), 6252–6259. https://doi.org/10.26355/eurrev_201810_16032 (2018).
doi: 10.26355/eurrev_201810_16032
pubmed: 30338790
Nakata, K. et al. Micro RNA-373 is down-regulated in pancreatic cancer and inhibits cancer cell invasion. Ann. Surg. Oncol. 21(Suppl 4), S564–S574. https://doi.org/10.1245/s10434-014-3676-8 (2014).
doi: 10.1245/s10434-014-3676-8
pubmed: 24748127
Cho, W. J. et al. miR-372 regulates cell cycle and apoptosis of ags human gastric cancer cell line through direct regulation of LATS2. Mol. Cells 28(6), 521–527. https://doi.org/10.1007/s10059-009-0158-0 (2009).
doi: 10.1007/s10059-009-0158-0
pubmed: 19937137
Feber, A. et al. MicroRNA expression profiles of esophageal cancer. J. Thorac. Cardiovasc. Surg. 135(2), 255–260. https://doi.org/10.1016/j.jtcvs.2007.08.055 (2008).
doi: 10.1016/j.jtcvs.2007.08.055
pubmed: 18242245
Xifeng, L. et al. Expression and function of miR-373 in human hepatocellular carcinoma. J. Kunming Med. Univ. 39(12), 5 (2018).
Wang, L. Q. et al. miR-372 and miR-373 enhance the stemness of colorectal cancer cells by repressing differentiation signaling pathways. Mol. Oncol. 12(11), 1949–1964. https://doi.org/10.1002/1878-0261.12376 (2018).
doi: 10.1002/1878-0261.12376
pubmed: 30171794
pmcid: 6210048
Brînzan, C., Aşchie, M., Cozaru, G., Dumitru, E. & Mitroi, A. The diagnostic value of miR-92a, -143, and -145 expression levels in patients with colorectal adenocarcinoma from Romania. Medicine 99(35), e21895. https://doi.org/10.1097/MD.0000000000021895 (2020).
doi: 10.1097/MD.0000000000021895
pubmed: 32871920
pmcid: 7458237
Gomes, S. E. et al. miR-143 or miR-145 overexpression increases cetuximab-mediated antibody-dependent cellular cytotoxicity in human colon cancer cells. Oncotarget 7(8), 9368–9387. https://doi.org/10.18632/oncotarget.7010 (2016).
doi: 10.18632/oncotarget.7010
pubmed: 26824186
pmcid: 4891046
Dong, Y. Z. & Hu, T. Effects of miR-143 overexpression on proliferation, apoptosis, EGFR and downstream signaling pathways in PC9/GR cell line. Eur. Rev. Med. Pharmacol. Sci. 22(6), 1709–1716. https://doi.org/10.26355/eurrev_201803_14584 (2018).
doi: 10.26355/eurrev_201803_14584
pubmed: 29630116
Zhang, T., Wang, K., Luo, H. et al. Expression changes and correlation analysis of miR-141-3p and its target genes in plasma of colorectal cancer patients. Chongqing Med. 48(01), 76–79 (2019).
Wu, S., Aksoy, M., Shi, J. & Houbaviy, H. B. Evolution of the miR-290-295/miR-371-373 cluster family seed repertoire. PloS One 9(9), e108519. https://doi.org/10.1371/journal.pone.0108519 (2014).
doi: 10.1371/journal.pone.0108519
pubmed: 25268927
pmcid: 4182485
Cooper, L. A., Shen, T. L. & Guan, J. L. Regulation of focal adhesion kinase by its amino-terminal domain through an autoinhibitory interaction. Mol. Cell. Biol. 23(22), 8030–8041. https://doi.org/10.1128/MCB.23.22.8030-8041.2003 (2003).
doi: 10.1128/MCB.23.22.8030-8041.2003
pubmed: 14585964
pmcid: 262338
Cicchini, C. et al. TGFbeta-induced EMT requires focal adhesion kinase (FAK) signaling. Exp. Cell Res. 314(1), 143–152. https://doi.org/10.1016/j.yexcr.2007.09.005 (2008).
doi: 10.1016/j.yexcr.2007.09.005
pubmed: 17949712
Hutvágner, G. et al. A cellular function for the RNA-interference enzyme Dicer in the maturation of the let-7 small temporal RNA. Science 293(5531), 834–838. https://doi.org/10.1126/science.1062961 (2001).
doi: 10.1126/science.1062961
pubmed: 11452083
Yuanping, T. et al. Study on the inhibition of liver cancer proliferation and metastasis ability by miR-373-3p targeting YWHAZ. Chin. J. Oncol. 7, 8 (2019).
Lee, Y. et al. MicroRNA genes are transcribed by RNA polymerase II. EMBO J. 23(20), 4051–4060. https://doi.org/10.1038/sj.emboj.7600385 (2004).
doi: 10.1038/sj.emboj.7600385
pubmed: 15372072
pmcid: 524334
Place, R. F., Li, L. C., Pookot, D., Noonan, E. J. & Dahiya, R. MicroRNA-373 induces expression of genes with complementary promoter sequences. Proc. Natl. Acad. Sci. U.S.A. 105(5), 1608–1613. https://doi.org/10.1073/pnas.0707594105 (2008).
doi: 10.1073/pnas.0707594105
pubmed: 18227514
pmcid: 2234192
Zhang, Y. et al. MiR-373 targeting of the Rab22a oncogene suppresses tumor invasion and metastasis in ovarian cancer. Oncotarget 5(23), 12291–12303. https://doi.org/10.18632/oncotarget.2577 (2014).
doi: 10.18632/oncotarget.2577
pubmed: 25460499
pmcid: 4323008
Jean, C. et al. Inhibition of endothelial FAK activity prevents tumor metastasis by enhancing barrier function. J. Cell Biol. 204(2), 247–263. https://doi.org/10.1083/jcb.201307067 (2014).
doi: 10.1083/jcb.201307067
pubmed: 24446483
pmcid: 3897185
Zhang, Y. et al. Identification of transgelin-2 as a biomarker of colorectal cancer by laser capture microdissection and quantitative proteome analysis. Cancer Sci. 101(2), 523–529. https://doi.org/10.1111/j.1349-7006.2009.01424.x (2010).
doi: 10.1111/j.1349-7006.2009.01424.x
pubmed: 19930159
Bonni, A. et al. Cell survival promoted by the Ras-MAPK signaling pathway by transcription-dependent and -independent mechanisms. Science 286(5443), 1358–1362. https://doi.org/10.1126/science.286.5443.1358 (1999).
doi: 10.1126/science.286.5443.1358
pubmed: 10558990
Wang, X., Wang, Q., Hu, W. & Evers, B. M. Regulation of phorbol ester-mediated TRAF1 induction in human colon cancer cells through a PKC/RAF/ERK/NF-kappaB-dependent pathway. Oncogene 23(10), 1885–1895. https://doi.org/10.1038/sj.onc.1207312 (2004).
doi: 10.1038/sj.onc.1207312
pubmed: 14981539
Jung, O. et al. Tetraspan TM4SF5-dependent direct activation of FAK and metastatic potential of hepatocarcinoma cells. J. Cell Sci. 125(Pt 24), 5960–5973. https://doi.org/10.1242/jcs.100586 (2012).
doi: 10.1242/jcs.100586
pubmed: 23077174
pmcid: 4074290
Lan, Y. T. et al. Mutations in the RAS and PI3K pathways are associated with metastatic location in colorectal cancers. J. Surg. Oncol. 111(7), 905–910. https://doi.org/10.1002/jso.23895 (2015).
doi: 10.1002/jso.23895
pubmed: 25920435
Song, G. et al. TIMP1 is a prognostic marker for the progression and metastasis of colon cancer through FAK-PI3K/AKT and MAPK pathway. J. Exp. Clin. Cancer Res. CR 35(1), 148. https://doi.org/10.1186/s13046-016-0427-7 (2016).
doi: 10.1186/s13046-016-0427-7
pubmed: 27644693