MicroRNA-503-5p Inhibits the CD97-Mediated JAK2/STAT3 Pathway in Metastatic or Paclitaxel-Resistant Ovarian Cancer Cells

Overview

Journal Neoplasia

Publisher Elsevier

Specialty Oncology

Date 2019 Jan 10

PMID 30622051

Citations 38

Authors

Ga Bin Park

Daejin Kim

Affiliations

Soon will be listed here.

Abstract

CD97 shows a strong relationship with metastasis and poor clinical outcome in various tumors, including ovarian cancer. The expression of CD97 in metastatic ovarian cancer cells was higher than that in primary ovarian cancer cells. Mature miRNAs are frequently de-regulated in cancer and incorporated into a specific mRNA, leading to post-transcriptional silencing. In this study, we investigated whether the miR-503-5p targeting of the CD97 3'-untranslated region (3'-UTR) contributes to ovarian cancer metastasis as well as the underlying mechanism regulating cancer progression. In LPS-stimulated or paclitaxel-resistant ovarian cancer cells, stimulation with recombinant human CD55 (rhCD55) of CD97 in ovarian cancer cells activated NF-κB-dependent miR-503-5p down-regulation and the JAK2/STAT3 pathway, consequently promoting the migratory and invasive capacity. Furthermore, restoration of miR-503-5p by transfection with mimics or NF-κB inhibitor efficiently blocked CD97 expression and the downstream JAK2/STAT3 signaling pathway. Target inhibition of JAK with siRNA also impaired colony formation and metastasis of LPS-stimulated and paclitaxel-resistant ovarian cancer cells. Taken together, these results suggest that high CD97 expression, which is controlled through the NF-κB/miR-503-5p signaling pathway, plays an important role in the invasive activity of metastatic and drug-resistant ovarian cancer cells by activating the JAK2/STAT3 pathway.

Citing Articles

Proteomic landscape of epithelial ovarian cancer.

Qian L, Zhu J, Xue Z, Zhou Y, Xiang N, Xu H Nat Commun. 2024; 15(1):6462.

PMID: 39085232 PMC: 11291745. DOI: 10.1038/s41467-024-50786-z.

Cell surface CD55 traffics to the nucleus leading to cisplatin resistance and stemness by inducing PRC2 and H3K27 trimethylation on chromatin in ovarian cancer.

Bharti R, Dey G, Khan D, Myers A, Huffman O, Saygin C Mol Cancer. 2024; 23(1):121.

PMID: 38853277 PMC: 11163727. DOI: 10.1186/s12943-024-02028-5.

Drug resistance in ovarian cancer: from mechanism to clinical trial.

Wang L, Wang X, Zhu X, Zhong L, Jiang Q, Wang Y Mol Cancer. 2024; 23(1):66.

PMID: 38539161 PMC: 10976737. DOI: 10.1186/s12943-024-01967-3.

miRNA Expression Profiles in Ovarian Endometriosis and Two Types of Ovarian Cancer-Endometriosis-Associated Ovarian Cancer and High-Grade Ovarian Cancer.

Szubert M, Nowak-Gluck A, Domanska-Senderowska D, Szymanska B, Sowa P, Rycerz A Int J Mol Sci. 2023; 24(24).

PMID: 38139300 PMC: 10743418. DOI: 10.3390/ijms242417470.

Tephrosin Suppresses the Chemoresistance of Paclitaxel-Resistant Ovarian Cancer via Inhibition of FGFR1 Signaling Pathway.

Kim H, Bae S, Lim Y, So K, Kim T, Bae S Biomedicines. 2023; 11(12).

PMID: 38137377 PMC: 10740824. DOI: 10.3390/biomedicines11123155.

References

Aust G, Steinert M, Schutz A, Boltze C, Wahlbuhl M, Hamann J . CD97, but not its closely related EGF-TM7 family member EMR2, is expressed on gastric, pancreatic, and esophageal carcinomas. Am J Clin Pathol. 2002; 118(5):699-707. DOI: 10.1309/A6AB-VF3F-7M88-C0EJ. View

Wobus M, Vogel B, Schmucking E, Hamann J, Aust G . N-glycosylation of CD97 within the EGF domains is crucial for epitope accessibility in normal and malignant cells as well as CD55 ligand binding. Int J Cancer. 2004; 112(5):815-22. DOI: 10.1002/ijc.20483. View

Esquela-Kerscher A, Slack F . Oncomirs - microRNAs with a role in cancer. Nat Rev Cancer. 2006; 6(4):259-69. DOI: 10.1038/nrc1840. View

Kelly M, Alvero A, Chen R, Silasi D, Abrahams V, Chan S . TLR-4 signaling promotes tumor growth and paclitaxel chemoresistance in ovarian cancer. Cancer Res. 2006; 66(7):3859-68. DOI: 10.1158/0008-5472.CAN-05-3948. View

Calin G, Croce C . MicroRNA signatures in human cancers. Nat Rev Cancer. 2006; 6(11):857-66. DOI: 10.1038/nrc1997. View

Rosen D, Mercado-Uribe I, Yang G, Bast Jr R, Amin H, Lai R . The role of constitutively active signal transducer and activator of transcription 3 in ovarian tumorigenesis and prognosis. Cancer. 2006; 107(11):2730-40. DOI: 10.1002/cncr.22293. View

Galle J, Sittig D, Hanisch I, Wobus M, Wandel E, Loeffler M . Individual cell-based models of tumor-environment interactions: Multiple effects of CD97 on tumor invasion. Am J Pathol. 2006; 169(5):1802-11. PMC: 1780199. DOI: 10.2353/ajpath.2006.060006. View

Yona S, Lin H, Siu W, Gordon S, Stacey M . Adhesion-GPCRs: emerging roles for novel receptors. Trends Biochem Sci. 2008; 33(10):491-500. DOI: 10.1016/j.tibs.2008.07.005. View

Friedman R, Farh K, Burge C, Bartel D . Most mammalian mRNAs are conserved targets of microRNAs. Genome Res. 2008; 19(1):92-105. PMC: 2612969. DOI: 10.1101/gr.082701.108. View

10.

Colomiere M, Ward A, Riley C, Trenerry M, Cameron-Smith D, Findlay J . Cross talk of signals between EGFR and IL-6R through JAK2/STAT3 mediate epithelial-mesenchymal transition in ovarian carcinomas. Br J Cancer. 2008; 100(1):134-44. PMC: 2634691. DOI: 10.1038/sj.bjc.6604794. View

11.

Croce C . Causes and consequences of microRNA dysregulation in cancer. Nat Rev Genet. 2009; 10(10):704-14. PMC: 3467096. DOI: 10.1038/nrg2634. View

12.

Hennessy B, Coleman R, Markman M . Ovarian cancer. Lancet. 2009; 374(9698):1371-82. DOI: 10.1016/S0140-6736(09)61338-6. View

13.

Lei L, Jin S, Gonzalez G, Behringer R, Woodruff T . The regulatory role of Dicer in folliculogenesis in mice. Mol Cell Endocrinol. 2009; 315(1-2):63-73. PMC: 2814883. DOI: 10.1016/j.mce.2009.09.021. View

14.

Szajnik M, Szczepanski M, Czystowska M, Elishaev E, Mandapathil M, Nowak-Markwitz E . TLR4 signaling induced by lipopolysaccharide or paclitaxel regulates tumor survival and chemoresistance in ovarian cancer. Oncogene. 2009; 28(49):4353-63. PMC: 2794996. DOI: 10.1038/onc.2009.289. View

15.

Han S, Xu C, Wu X, Li J, Liu Z, Zeng Q . The impact of expressions of CD97 and its ligand CD55 at the invasion front on prognosis of rectal adenocarcinoma. Int J Colorectal Dis. 2010; 25(6):695-702. DOI: 10.1007/s00384-010-0926-5. View

16.

Ahmed N, Abubaker K, Findlay J, Quinn M . Epithelial mesenchymal transition and cancer stem cell-like phenotypes facilitate chemoresistance in recurrent ovarian cancer. Curr Cancer Drug Targets. 2010; 10(3):268-78. DOI: 10.2174/156800910791190175. View

17.

Jinawath N, Vasoontara C, Jinawath A, Fang X, Zhao K, Yap K . Oncoproteomic analysis reveals co-upregulation of RELA and STAT5 in carboplatin resistant ovarian carcinoma. PLoS One. 2010; 5(6):e11198. PMC: 2887843. DOI: 10.1371/journal.pone.0011198. View

18.

Caporali A, Meloni M, Vollenkle C, Bonci D, Sala-Newby G, Addis R . Deregulation of microRNA-503 contributes to diabetes mellitus-induced impairment of endothelial function and reparative angiogenesis after limb ischemia. Circulation. 2011; 123(3):282-91. DOI: 10.1161/CIRCULATIONAHA.110.952325. View

19.

Kumar S, Mahdi H, Bryant C, Shah J, Garg G, Munkarah A . Clinical trials and progress with paclitaxel in ovarian cancer. Int J Womens Health. 2011; 2:411-27. PMC: 3024893. DOI: 10.2147/IJWH.S7012. View

20.

Plaisance-Bonstaff K, Renne R . Viral miRNAs. Methods Mol Biol. 2011; 721:43-66. DOI: 10.1007/978-1-61779-037-9_3. View