WWC1, a target of miR-138-5p, facilitates the progression of prostate cancer

Published:August 11, 2022DOI:



      WWC1 is known to be involved in the development of cancer. Therefore, it is critical to study the molecular mechanisms and cellular roles of WWC1 in cancer therapy.


      In this study, we examined the effect of WWC1 on prostate cancer tumorigenesis and the role of miR-138-5p in prostate cancer. The expression levels of miR-138-5p and WWC1 in prostate cancer (Pca) tissues and cells were detected by real-time quantitative reverse transcription PCR and western blotting. Cell counting kit-8 and BrdU assays were performed to study cell proliferation and caspase-3 activity assay to detect apoptosis. Migration experiments were conducted to observe the movement ability of the cells.


      The expression of WWC1 in Pca tissues or cell lines was increased, whereas miR-138-5p expression was decreased. MiR-138-5p targeted and partially neutralized the role of WWC1 in Pca cells. Moreover, reduced expression of WWC1 in Pca cell lines suppressed cell proliferation and migration and promoted apoptosis in vitro.


      Collectively, these findings reveal a novel mechanism by which miR-138-5p negatively regulates WWC1 in Pca.

      Key Indexing Terms

      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'


      Subscribe to The American Journal of the Medical Sciences
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • Siegel RL
        • Miller KD
        • Jemal A.
        Cancer statistics.
        CA Cancer J Clin. 2019; 69 (2019): 7-34
        • Zhao H
        • Zhao X
        • Lei T
        • Zhang M.
        Screening, identification of prostate cancer urinary biomarkers and verification of important spots.
        Investig New Drugs. 2019; 37: 935-947
        • Grubb RL
        • Pinsky PF
        • Greenlee RT
        • et al.
        Prostate cancer screening in the prostate, lung, colorectal and ovarian cancer screening trial: update on findings from the initial four rounds of screening in a randomized trial.
        BJU Int. 2008; 102 (3rd): 1524-1530
        • Chen J
        • Liu X
        • Ke K
        • et al.
        LINC00992 contributes to the oncogenic phenotypes in prostate cancer via targeting miR-3935 and augmenting GOLM1 expression.
        BMC Cancer. 2020; 20: 749
        • Heidenreich A
        • Bastian PJ
        • Bellmunt J
        • et al.
        EAU guidelines on prostate cancer. part 1: screening, diagnosis, and local treatment with curative intent-update.
        Eur Urol. 2014; 65 (2013): 124-137
        • Maughan BL
        • Antonarakis ES.
        Androgen pathway resistance in prostate cancer and therapeutic implications.
        Expert Opin Pharmacotherapy. 2015; 16: 1521-1537
        • Kremerskothen J
        • Plaas C
        • Büther K
        • et al.
        Characterization of KIBRA, a novel WW domain-containing protein.
        Biochem Biophys Res Commun. 2003; 300: 862-867
        • Lin T
        • Zhang L
        • Liu S
        • et al.
        WWC1 promotes podocyte survival via stabilizing slit diaphragm protein dendrin.
        Mol Med Rep. 2017; 16: 8685-8690
        • Moleirinho S
        • Chang N
        • Sims AH
        • et al.
        KIBRA exhibits MST-independent functional regulation of the Hippo signaling pathway in mammals.
        Oncogene. 2013; 32: 1821-1830
        • Stauffer S
        • Chen X
        • Zhang L
        • Chen Y
        • Dong J.
        KIBRA promotes prostate cancer cell proliferation and motility.
        FEBS J. 2016; 283: 1800-1811
        • Markou A
        • Tsaroucha EG
        • Kaklamanis L
        • Fotinou M
        • Georgoulias V
        • Lianidou ES.
        Prognostic value of mature microRNA-21 and microRNA-205 overexpression in non-small cell lung cancer by quantitative real-time RT-PCR.
        Clin Chem. 2008; 54: 1696-1704
        • Lebanony D
        • Benjamin H
        • Gilad S
        • et al.
        Diagnostic assay based on hsa-miR-205 expression distinguishes squamous from nonsquamous non-small-cell lung carcinoma.
        J Clin Oncol. 2009; 27: 2030-2037
        • Gregory PA
        • Bert AG
        • Paterson EL
        • et al.
        The miR-200 family and miR-205 regulate epithelial to mesenchymal transition by targeting ZEB1 and SIP1.
        Nat Cell Biol. 2008; 10: 593-601
        • Knyazev EN
        • Samatov TR
        • Fomicheva KA
        • Nyushko KM
        • Alekseev BY
        • Shkurnikov MY.
        MicroRNA hsa-miR-4674 in hemolysis-free blood plasma is associated with distant metastases of prostatic cancer.
        Bull Exp Biol Med. 2016; 161: 112-115
        • Dezhong L
        • Xiaoyi Z
        • Xianlian L
        • et al.
        miR-150 is a factor of survival in prostate cancer patients.
        J BUON : Off J Balkan Union Oncol. 2015; 20: 173-179
        • Erdmann K
        • Kaulke K
        • Rieger C
        • Salomo K
        • Wirth MP
        • Fuessel S.
        MiR-26a and miR-138 block the G1/S transition by targeting the cell cycle regulating network in prostate cancer cells.
        J Cancer Res Clin Oncol. 2016; 142: 2249-2261
        • Zhang D
        • Liu X
        • Zhang Q
        • Chen X.
        miR-138-5p inhibits the malignant progression of prostate cancer by targeting FOXC1.
        Cancer Cell Int. 2020; 20: 297
        • Wang F
        • Wang W
        • Lu L
        • et al.
        MicroRNA‑16‑5p regulates cell survival, cell cycle and apoptosis by targeting AKT3 in prostate cancer cells.
        Oncol Rep. 2020; 44: 1282-1292
        • Wu J
        • Ji A
        • Wang X
        • et al.
        MicroRNA-195-5p, a new regulator of Fra-1, suppresses the migration and invasion of prostate cancer cells.
        J Transl Med. 2015; 13: 289
        • Xiong Y
        • Zhang J
        • Song C.
        CircRNA ZNF609 functions as a competitive endogenous RNA to regulate FOXP4 expression by sponging miR-138-5p in renal carcinoma.
        J Cell Physiol. 2019; 234: 10646-10654
        • Zhao L
        • Yu H
        • Yi S
        • et al.
        The tumor suppressor miR-138-5p targets PD-L1 in colorectal cancer.
        Oncotarget. 2016; 7: 45370-45384
        • Ou L
        • Wang D
        • Zhang H
        • Yu Q
        • Hua F.
        Decreased expression of miR-138-5p by lncRNA H19 in cervical cancer promotes tumor proliferation.
        Oncol Res. 2018; 26: 401-410
        • Dong P
        • Xiong Y
        • Watari H
        • et al.
        MiR-137 and miR-34a directly target Snail and inhibit EMT, invasion and sphere-forming ability of ovarian cancer cells.
        J Exp Clin Cancer Res. 2016; 35: 132
        • Zhou PJ
        • Xue W
        • Peng J
        • et al.
        Elevated expression of Par3 promotes prostate cancer metastasis by forming a Par3/aPKC/KIBRA complex and inactivating the hippo pathway.
        J Exp Clin Cancer Res. 2017; 36: 139