MicroRNA-214 Targets PTK6 to Inhibit Tumorigenic Potential and Increase Drug Sensitivity of Prostate Cancer Cells

Overview

Journal Sci Rep

Specialty Science

Date 2019 Jul 7

PMID 31278310

Citations 23

Authors

Patrice Cagle

Suryakant Niture

Anvesha Srivastava

Malathi Ramalinga

Rasha Aqeel

Leslimar Rios-Colon

Uchechukwu Chimeh

Simeng Suy

Sean P Collins

Rajvir Dahiya

Deepak Kumar

Affiliations

Soon will be listed here.

Abstract

Prostate cancer is the most commonly diagnosed cancer in men with African American men disproportionally suffering from the burden of this disease. Biomarkers that could discriminate indolent from aggressive and drug resistance disease are lacking. MicroRNAs are small non-coding RNAs that affect numerous physiological and pathological processes, including cancer development and have been suggested as biomarkers and therapeutic targets. In the present study, we investigated the role of miR-214 on prostate cancer cell survival/migration/invasion, cell cycle regulation, and apoptosis. miR-214 was differentially expressed between Caucasian and African American prostate cancer cells. Importantly, miR-214 overexpression in prostate cancer cells induced apoptosis, inhibiting cell proliferation and colony forming ability. miR-214 expression in prostate cancer cells also inhibited cell migration and 3D spheroid invasion. Mechanistically, miR-214 inhibited prostate cancer cell proliferation by targeting protein tyrosine kinase 6 (PTK6). Restoration of PTK6 expression attenuated the inhibitory effect of miR-214 on cell proliferation. Moreover, simultaneous inhibition of PTK6 by ibrutinib and miR-214 significantly reduced cell proliferation/survival. Our data indicates that miR-214 could act as a tumor suppressor in prostate cancer and could potentially be utilized as a biomarker and therapeutic target.

Citing Articles

MiR-34c-5p Inhibition Affects Bax/Bcl2 Expression and Reverses Bortezomib Resistance in Multiple Myeloma Cells.

Matour E, Tahannejad Asadi Z, Deilami A, Azandeh S, Taheri B Indian J Hematol Blood Transfus. 2024; 40(4):596-603.

PMID: 39469181 PMC: 11512978. DOI: 10.1007/s12288-024-01742-w.

Assessing the Potential of Small Peptides for Altering Expression Levels of the Iron-Regulatory Genes and and Enhancing Androgen Receptor Inhibitor Activity in In Vitro Prostate Cancer Models.

Currie C, Bjerknes C, Myklebust T, Framroze B Int J Mol Sci. 2023; 24(20).

PMID: 37894914 PMC: 10607736. DOI: 10.3390/ijms242015231.

Deregulated microRNAs Involved in Prostate Cancer Aggressiveness and Treatment Resistance Mechanisms.

Gujrati H, Ha S, Wang B Cancers (Basel). 2023; 15(12).

PMID: 37370750 PMC: 10296615. DOI: 10.3390/cancers15123140.

Characterisation of cell lines derived from prostate cancer patients with localised disease.

Moya L, Walpole C, Rae F, Srinivasan S, Seim I, Lai J Prostate Cancer Prostatic Dis. 2023; 26(3):614-624.

PMID: 37264224 PMC: 10449630. DOI: 10.1038/s41391-023-00679-x.

MicroRNA-483-5p Inhibits Hepatocellular Carcinoma Cell Proliferation, Cell Steatosis, and Fibrosis by Targeting PPARα and TIMP2.

Niture S, Gadi S, Qi Q, Gyamfi M, Varghese R, Rios-Colon L Cancers (Basel). 2023; 15(6).

PMID: 36980601 PMC: 10046356. DOI: 10.3390/cancers15061715.

References

Chen D, Wang Z, Zeng Z, Wu W, Zhang D, Luo H . Identification of microRNA-214 as a negative regulator of colorectal cancer liver metastasis by way of regulation of fibroblast growth factor receptor 1 expression. Hepatology. 2014; 60(2):598-609. DOI: 10.1002/hep.27118. View

Wang F, Li L, Chen Z, Zhu M, Gu Y . MicroRNA-214 acts as a potential oncogene in breast cancer by targeting the PTEN-PI3K/Akt signaling pathway. Int J Mol Med. 2016; 37(5):1421-8. DOI: 10.3892/ijmm.2016.2518. View

Niture S, Ramalinga M, Kedir H, Patacsil D, Niture S, Li J . TNFAIP8 promotes prostate cancer cell survival by inducing autophagy. Oncotarget. 2018; 9(42):26884-26899. PMC: 6003558. DOI: 10.18632/oncotarget.25529. View

Huang S, Yuan Y, Zhuang C, Li B, Gong D, Wang S . MicroRNA-98 and microRNA-214 post-transcriptionally regulate enhancer of zeste homolog 2 and inhibit migration and invasion in human esophageal squamous cell carcinoma. Mol Cancer. 2012; 11:51. PMC: 3496689. DOI: 10.1186/1476-4598-11-51. View

Karakas C, Wang C, Deng F, Huang H, Wang D, Lee P . Molecular mechanisms involving prostate cancer racial disparity. Am J Clin Exp Urol. 2017; 5(3):34-48. PMC: 5698597. View

Jansson M, Lund A . MicroRNA and cancer. Mol Oncol. 2012; 6(6):590-610. PMC: 5528350. DOI: 10.1016/j.molonc.2012.09.006. View

Wu H, Wang A, Zhang W, Wang B, Chen C, Wang W . Ibrutinib selectively and irreversibly targets EGFR (L858R, Del19) mutant but is moderately resistant to EGFR (T790M) mutant NSCLC Cells. Oncotarget. 2015; 6(31):31313-22. PMC: 4741607. DOI: 10.18632/oncotarget.5182. View

Xu X, Ye Y, Wu Z, He Q, Tan L, Xiao K . Overexpression of PTK6 predicts poor prognosis in bladder cancer patients. J Cancer. 2017; 8(17):3464-3473. PMC: 5687160. DOI: 10.7150/jca.21318. View

OKeefe E, Meltzer J, Bethea T . Health disparities and cancer: racial disparities in cancer mortality in the United States, 2000-2010. Front Public Health. 2015; 3:51. PMC: 4398881. DOI: 10.3389/fpubh.2015.00051. View

10.

Hanahan D, Weinberg R . Hallmarks of cancer: the next generation. Cell. 2011; 144(5):646-74. DOI: 10.1016/j.cell.2011.02.013. View

11.

Mitchell P, Barker K, Martindale J, Kamalati T, Lowe P, Page M . Cloning and characterisation of cDNAs encoding a novel non-receptor tyrosine kinase, brk, expressed in human breast tumours. Oncogene. 1994; 9(8):2383-90. View

12.

Ostrander J, Daniel A, Lange C . Brk/PTK6 signaling in normal and cancer cell models. Curr Opin Pharmacol. 2010; 10(6):662-9. PMC: 2981671. DOI: 10.1016/j.coph.2010.08.007. View

13.

Rupaimoole R, Calin G, Lopez-Berestein G, Sood A . miRNA Deregulation in Cancer Cells and the Tumor Microenvironment. Cancer Discov. 2016; 6(3):235-46. PMC: 4783232. DOI: 10.1158/2159-8290.CD-15-0893. View

14.

Melo S, Esteller M . Dysregulation of microRNAs in cancer: playing with fire. FEBS Lett. 2010; 585(13):2087-99. DOI: 10.1016/j.febslet.2010.08.009. View

15.

Yang Z, Chen S, Luan X, Li Y, Liu M, Li X . MicroRNA-214 is aberrantly expressed in cervical cancers and inhibits the growth of HeLa cells. IUBMB Life. 2009; 61(11):1075-82. DOI: 10.1002/iub.252. View

16.

Xia H, Ooi L, Hui K . MiR-214 targets β-catenin pathway to suppress invasion, stem-like traits and recurrence of human hepatocellular carcinoma. PLoS One. 2012; 7(9):e44206. PMC: 3433464. DOI: 10.1371/journal.pone.0044206. View

17.

Siegel R, Miller K, Jemal A . Cancer statistics, 2018. CA Cancer J Clin. 2018; 68(1):7-30. DOI: 10.3322/caac.21442. View

18.

Brauer P, Tyner A . Building a better understanding of the intracellular tyrosine kinase PTK6 - BRK by BRK. Biochim Biophys Acta. 2010; 1806(1):66-73. PMC: 2885473. DOI: 10.1016/j.bbcan.2010.02.003. View

19.

Wozniak D, Kajdacsy-Balla A, Macias V, Ball-Kell S, Zenner M, Bie W . PTEN is a protein phosphatase that targets active PTK6 and inhibits PTK6 oncogenic signaling in prostate cancer. Nat Commun. 2017; 8(1):1508. PMC: 5688148. DOI: 10.1038/s41467-017-01574-5. View

20.

Chandrasekaran K, Sathyanarayanan A, Karunagaran D . MicroRNA-214 suppresses growth, migration and invasion through a novel target, high mobility group AT-hook 1, in human cervical and colorectal cancer cells. Br J Cancer. 2016; 115(6):741-51. PMC: 5023773. DOI: 10.1038/bjc.2016.234. View