Sensitizes Ovarian Cancer Cells to Irradiation by Inhibiting and Attenuating Autophagy

Overview

Journal Mol Ther Nucleic Acids

Publisher Cell Press

Date 2021 Mar 5

PMID 33664992

Citations 6

Authors

Lingling Wang

Ying Liu

Haixia Li

Cui Zhang

Hongbo Wang

Shaochun Dai

Wen Cheng

Yan Sun

Xiulan Zheng

Affiliations

Soon will be listed here.

Abstract

Ovarian cancer (OC) is a type of cancer with high prevalence and shocking mortality in women around the world. Radioresistance is a major reason for OC relapse. Mounting studies have shown the significant function of dysregulated microRNAs (miRNAs) in cancer progression and the cellular response to irradiation. The present study inquired about the function and mechanism of microRNA () in regulating radiosensitivity of OC cells. Results showed that was downregulated in OC, and a low level indicated a disappointing prognosis for OC patients. Besides, in OC cells exposed to irradiation, the expression of decreased over time. Functionally, the upregulation of retarded OC cell proliferation and sensitized OC cells to irradiation. Mechanistically, targeted and inhibited fused in sarcoma (). Additionally, was upregulated in OC and its expression further elevated in OC cells under irradiation. Furthermore, targeted to inhibit autophagy, therefore sensitizing OC cells to irradiation. Collectively, our study uncovered as a novel radiosensitizer by targeting in OC cells, which may shed a new light on developing targets for treating patients with OC, particularly those with radioresistance.

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References

Ke H, Zhao L, Feng X, Xu H, Zou L, Yang Q . NEAT1 is Required for Survival of Breast Cancer Cells Through FUS and miR-548. Gene Regul Syst Bio. 2016; 10(Suppl 1):11-7. PMC: 4849421. DOI: 10.4137/GRSB.S29414. View

Rai B, Bansal A, Patel F, Sharma S . Radiotherapy for ovarian cancers - redefining the role. Asian Pac J Cancer Prev. 2014; 15(12):4759-63. DOI: 10.7314/apjcp.2014.15.12.4759. View

Wang Z, Lei H, Sun Q . MicroRNA-141 and its associated gene FUS modulate proliferation, migration and cisplatin chemosensitivity in neuroblastoma cell lines. Oncol Rep. 2016; 35(5):2943-51. PMC: 4811401. DOI: 10.3892/or.2016.4640. View

Yahara K, Ohguri T, Imada H, Yamaguchi S, Kawagoe T, Matsuura Y . Epithelial ovarian cancer: definitive radiotherapy for limited recurrence after complete remission had been achieved with aggressive front-line therapy. J Radiat Res. 2012; 54(2):322-9. PMC: 3589945. DOI: 10.1093/jrr/rrs108. View

Hu J, He G, Lan X, Zeng Z, Guan J, Ding Y . Inhibition of ATG12-mediated autophagy by miR-214 enhances radiosensitivity in colorectal cancer. Oncogenesis. 2018; 7(2):16. PMC: 5833763. DOI: 10.1038/s41389-018-0028-8. View

Rabbitts T, Forster A, Larson R, Nathan P . Fusion of the dominant negative transcription regulator CHOP with a novel gene FUS by translocation t(12;16) in malignant liposarcoma. Nat Genet. 1993; 4(2):175-80. DOI: 10.1038/ng0693-175. View

Li B, Lu W, Qu J, Ye L, Du G, Wan X . Loss of exosomal miR-148b from cancer-associated fibroblasts promotes endometrial cancer cell invasion and cancer metastasis. J Cell Physiol. 2018; 234(3):2943-2953. DOI: 10.1002/jcp.27111. View

Ghanbari R, Mosakhani N, Asadi J, Nouraee N, Mowla S, Poustchi H . Decreased expression of fecal miR-4478 and miR-1295b-3p in early-stage colorectal cancer. Cancer Biomark. 2014; 15(2):189-95. DOI: 10.3233/CBM-140453. View

Ma H, Zheng S, Zhang X, Gong T, Lv X, Fu S . High mobility group box 1 promotes radioresistance in esophageal squamous cell carcinoma cell lines by modulating autophagy. Cell Death Dis. 2019; 10(2):136. PMC: 6372718. DOI: 10.1038/s41419-019-1355-1. View

10.

Ryu H, Jun M, Min K, Jang D, Lee Y, Kim H . Autophagy regulates amyotrophic lateral sclerosis-linked fused in sarcoma-positive stress granules in neurons. Neurobiol Aging. 2014; 35(12):2822-2831. DOI: 10.1016/j.neurobiolaging.2014.07.026. View

11.

Schickel R, Boyerinas B, Park S, Peter M . MicroRNAs: key players in the immune system, differentiation, tumorigenesis and cell death. Oncogene. 2008; 27(45):5959-74. DOI: 10.1038/onc.2008.274. View

12.

Hussein M . Nontraditional cytotoxic therapies for relapsed/refractory multiple myeloma. Oncologist. 2002; 7 Suppl 1:20-9. DOI: 10.1634/theoncologist.7-suppl_1-20. View

13.

Soo K, Sultana J, King A, Atkinson R, Warraich S, Sundaramoorthy V . ALS-associated mutant FUS inhibits macroautophagy which is restored by overexpression of Rab1. Cell Death Discov. 2016; 1:15030. PMC: 4979432. DOI: 10.1038/cddiscovery.2015.30. View

14.

Crozat A, Aman P, Mandahl N, Ron D . Fusion of CHOP to a novel RNA-binding protein in human myxoid liposarcoma. Nature. 1993; 363(6430):640-4. DOI: 10.1038/363640a0. View

15.

Beresneva E, Rykov S, Hodyrev D, Pronina I, Ermilova V, Kazubskaia T . [Methylation profile of group of miRNA genes in clear cell renal cell carcinoma; involvement in cancer progression]. Genetika. 2013; 49(3):366-75. DOI: 10.7868/s001667581303003x. View

16.

Weidhaas J, Babar I, Nallur S, Trang P, Roush S, Boehm M . MicroRNAs as potential agents to alter resistance to cytotoxic anticancer therapy. Cancer Res. 2007; 67(23):11111-6. PMC: 6070379. DOI: 10.1158/0008-5472.CAN-07-2858. View

17.

Siegel R, Miller K, Jemal A . Cancer statistics, 2015. CA Cancer J Clin. 2015; 65(1):5-29. DOI: 10.3322/caac.21254. View

18.

Morohoshi F, Ootsuka Y, Arai K, Ichikawa H, Mitani S, Munakata N . Genomic structure of the human RBP56/hTAFII68 and FUS/TLS genes. Gene. 1998; 221(2):191-8. DOI: 10.1016/s0378-1119(98)00463-6. View

19.

Ghanbari R, Rezasoltani S, Hashemi J, Mohamadkhani A, Tahmasebifar A, Arefian E . Expression Analysis of Previously Verified Fecal and Plasma Dow-regulated MicroRNAs (miR-4478, 1295-3p, 142-3p and 26a-5p), in FFPE Tissue Samples of CRC Patients. Arch Iran Med. 2017; 20(2):92-95. DOI: 0172002/AIM.006. View

20.

Niemoeller O, Niyazi M, Corradini S, Zehentmayr F, Li M, Lauber K . MicroRNA expression profiles in human cancer cells after ionizing radiation. Radiat Oncol. 2011; 6:29. PMC: 3079656. DOI: 10.1186/1748-717X-6-29. View