MicroRNA‑330 is downregulated in retinoblastoma and suppresses cell viability and invasion by directly targeting ROCK1

  • Authors:
    • Ling Wang
    • Lina Wang
    • Lin Li
    • Hong Zhang
    • Xueman Lyu
  • View Affiliations

  • Published online on: August 1, 2019     https://doi.org/10.3892/mmr.2019.10545
  • Pages: 3440-3447
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Abstract

Abnormal expression of microRNAs (miRNAs/miRs) has been previously reported in various types of human cancer, such as retinoblastoma (RB). Dysregulated miRNAs have been demonstrated to be important epigenetic regulators of numerous biological events associated with RB. Therefore, improved understanding of the precise roles of miRNAs in RB is required to develop novel therapeutic strategies for the treatment of patients with this disease. In the present study, reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR) was performed to detect miR‑330 expression in RB tissues and cell lines. The effects of miR‑330 overexpression on the viability and invasion of RB cells were determined using MTT and Matrigel®‑based invasion assays, respectively. The mechanisms underlying the activity of miR‑330 in RB cells were investigated via bioinformatics analysis, luciferase reporter assays, and RT‑qPCR and western blot analyses. It was revealed that the levels of miR‑330 expression were significantly downregulated in RB tissues and cell lines compared with in control healthy tissues and cells, respectively. Overexpression of miR‑330 in RB cells significantly reduced the viability and invasion of cells in vitro. Additionally, ρ‑associated coiled‑coil containing protein kinase 1 (ROCK1) was identified as a putative target of miR‑330 using bioinformatics analysis. Subsequent experiments revealed that miR‑330 interacted with the 3'‑untranslated region of ROCK1 and downregulated its expression in RB cells. Furthermore, the expression levels of ROCK1 were increased in RB tissues compared with healthy controls and negatively correlated with miR‑330 expression. Finally, upregulation of ROCK1 expression reversed the miR‑330‑induced inhibition of the viability and invasion of RB cells. Collectively, these results suggested that miR‑330 exhibits tumor‑suppressor activity in the development of RB by directly targeting ROCK1, indicating that restoration of miR‑330 expression may be a promising therapeutic technique in the treatment of patients with RB.

References

1 

Jabbour P, Chalouhi N, Tjoumakaris S, Gonzalez LF, Dumont AS, Chitale R, Rosenwasser R, Bianciotto CG and Shields C: Pearls and pitfalls of intraarterial chemotherapy for retinoblastoma. J Neurosurg Pediatr. 10:175–181. 2012. View Article : Google Scholar : PubMed/NCBI

2 

Kivelä T: The epidemiological challenge of the most frequent eye cancer: Retinoblastoma, an issue of birth and death. Br J Ophthalmol. 93:1129–1131. 2009. View Article : Google Scholar : PubMed/NCBI

3 

Abramson DH, Beaverson K, Sangani P, Vora RA, Lee TC, Hochberg HM, Kirszrot J and Ranjithan M: Screening for retinoblastoma: Presenting signs as prognosticators of patient and ocular survival. Pediatrics. 112:1248–1255. 2003. View Article : Google Scholar : PubMed/NCBI

4 

Meel R, Radhakrishnan V and Bakhshi S: Current therapy and recent advances in the management of retinoblastoma. Indian J Med Paediatr Oncol. 33:80–88. 2012. View Article : Google Scholar : PubMed/NCBI

5 

Abramson DH, Marr BP, Brodie S, Dunkel IJ and Gobin PY: Intraarterial chemotherapy for kissing macula tumors in retinoblastoma. Retin Cases Brief Rep. 6:209–211. 2012. View Article : Google Scholar : PubMed/NCBI

6 

Benavente CA and Dyer MA: Genetics and epigenetics of human retinoblastoma. Annu Rev Pathol. 10:547–562. 2015. View Article : Google Scholar : PubMed/NCBI

7 

Munker R and Calin GA: MicroRNA profiling in cancer. Clin Sci (Lond). 121:141–158. 2011. View Article : Google Scholar : PubMed/NCBI

8 

Zheng Y, Lu X, Xu L, Chen Z, Li Q and Yuan J: MicroRNA-675 promotes glioma cell proliferation and motility by negatively regulating retinoblastoma 1. Hum Pathol. 69:63–71. 2017. View Article : Google Scholar : PubMed/NCBI

9 

Bagnyukova TV, Pogribny IP and Chekhun VF: MicroRNAs in normal and cancer cells: A new class of gene expression regulators. Exp Oncol. 28:263–269. 2006.PubMed/NCBI

10 

Laengsri V, Kerdpin U, Plabplueng C, Treeratanapiboon L and Nuchnoi P: Cervical cancer markers: Epigenetics and microRNAs. Lab Med. 49:97–111. 2018. View Article : Google Scholar : PubMed/NCBI

11 

Lou W, Liu J, Gao Y, Zhong G, Chen D, Shen J, Bao C, Xu L, Pan J, Cheng J, et al: MicroRNAs in cancer metastasis and angiogenesis. Oncotarget. 8:115787–115802. 2017. View Article : Google Scholar : PubMed/NCBI

12 

Ramassone A, Pagotto S, Veronese A and Visone R: Epigenetics and MicroRNAs in cancer. Int J Mol Sci. 19(pii): E4592018. View Article : Google Scholar : PubMed/NCBI

13 

Golabchi K, Soleimani-Jelodar R, Aghadoost N, Momeni F, Moridikia A, Nahand JS, Masoudifar A, Razmjoo H and Mirzaei H: MicroRNAs in retinoblastoma: Potential diagnostic and therapeutic biomarkers. J Cell Physiol. 233:3016–3023. 2018. View Article : Google Scholar : PubMed/NCBI

14 

Singh U, Malik MA, Goswami S, Shukla S and Kaur J: Epigenetic regulation of human retinoblastoma. Tumour Biol. 37:14427–14441. 2016. View Article : Google Scholar : PubMed/NCBI

15 

Huang J, Yang Y, Fang F and Liu K: MALAT1 modulates the autophagy of retinoblastoma cell through miR-124-mediated stx17 regulation. J Cell Biochem. 119:3853–3863. 2018. View Article : Google Scholar : PubMed/NCBI

16 

Wang H, Chen SH, Kong P, Zhang LY, Zhang LL, Zhang NQ and Gu H: Increased expression of miR-330-3p: A novel independent indicator of poor prognosis in human breast cancer. Eur Rev Med Pharmacol Sci. 22:1726–1730. 2018.PubMed/NCBI

17 

Mesci A, Huang X, Taeb S, Jahangiri S, Kim Y, Fokas E, Bruce J, Leong HS and Liu SK: Targeting of CCBE1 by miR-330-3p in human breast cancer promotes metastasis. Br J Cancer. 116:1350–1357. 2017. View Article : Google Scholar : PubMed/NCBI

18 

Meng H, Wang K, Chen X, Guan X, Hu L, Xiong G, Li J and Bai Y: MicroRNA-330-3p functions as an oncogene in human esophageal cancer by targeting programmed cell death 4. Am J Cancer Res. 5:1062–1075. 2015.PubMed/NCBI

19 

Liu X, Shi H, Liu B, Li J, Liu Y and Yu B: miR-330-3p controls cell proliferation by targeting early growth response 2 in non-small-cell lung cancer. Acta Biochim Biophys Sin (Shanghai). 47:431–440. 2015. View Article : Google Scholar : PubMed/NCBI

20 

Wei CH, Wu G, Cai Q, Gao XC, Tong F, Zhou R, Zhang RG, Dong JH, Hu Y and Dong XR: MicroRNA-330-3p promotes cell invasion and metastasis in non-small cell lung cancer through GRIA3 by activating MAPK/ERK signaling pathway. J Hematol Oncol. 10:1252017. View Article : Google Scholar : PubMed/NCBI

21 

Qu S, Yao Y, Shang C, Xue Y, Ma J, Li Z and Liu Y: MicroRNA-330 is an oncogenic factor in glioblastoma cells by regulating SH3GL2 gene. PLoS One. 7:e460102012. View Article : Google Scholar : PubMed/NCBI

22 

Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods. 25:402–408. 2001. View Article : Google Scholar : PubMed/NCBI

23 

Wang J, Liu XH, Yang ZJ, Xie B and Zhong YS: The effect of ROCK-1 activity change on the adhesive and invasive ability of Y79 retinoblastoma cells. BMC Cancer. 14:892014. View Article : Google Scholar : PubMed/NCBI

24 

Wu S, Ai N, Liu Q and Zhang J: MicroRNA-448 inhibits the progression of retinoblastoma by directly targeting ROCK1 and regulating PI3K/AKT signalling pathway. Oncol Rep. 39:2402–2412. 2018.PubMed/NCBI

25 

Wang Z, Yao YJ, Zheng F, Guan Z, Zhang L, Dong N and Qin WJ: Mir-138-5p acts as a tumor suppressor by targeting pyruvate dehydrogenase kinase 1 in human retinoblastoma. Eur Rev Med Pharmacol Sci. 21:5624–5629. 2017.PubMed/NCBI

26 

Yang L, Wei N, Wang L, Wang X and Liu QH: miR-498 promotes cell proliferation and inhibits cell apoptosis in retinoblastoma by directly targeting CCPG1. Childs Nerv Syst. 34:417–422. 2018. View Article : Google Scholar : PubMed/NCBI

27 

Zhao Y, Zhang S and Zhang Y: MicroRNA-320 inhibits cell proliferation, migration and invasion in retinoblastoma by targeting specificity protein 1. Mol Med Rep. 16:2191–2198. 2017. View Article : Google Scholar : PubMed/NCBI

28 

Mao Y, Chen H, Lin Y, Xu X, Hu Z, Zhu Y, Wu J, Xu X, Zheng X and Xie L: microRNA-330 inhibits cell motility by downregulating Sp1 in prostate cancer cells. Oncol Rep. 30:327–333. 2013. View Article : Google Scholar : PubMed/NCBI

29 

Zheng Z, Bao F, Chen X, Huang H and Zhang X: MicroRNA-330-3p expression indicates good prognosis and suppresses cell proliferation by targeting Bmi-1 in osteosarcoma. Cell Physiol Biochem. 46:442–450. 2018. View Article : Google Scholar : PubMed/NCBI

30 

Xu W, Jiang H, Zhang F, Gao J and Hou J: MicroRNA-330 inhibited cell proliferation and enhanced chemosensitivity to 5-fluorouracil in colorectal cancer by directly targeting thymidylate synthase. Oncol Lett. 13:3387–3394. 2017. View Article : Google Scholar : PubMed/NCBI

31 

Zhang C, Zhang S, Zhang Z, He J, Xu Y and Liu S: ROCK has a crucial role in regulating prostate tumor growth through interaction with c-Myc. Oncogene. 33:5582–5591. 2014. View Article : Google Scholar : PubMed/NCBI

32 

Rossman KL, Der CJ and Sondek J: GEF means go: Turning on RHO GTPases with guanine nucleotide-exchange factors. Nat Rev Mol Cell Biol. 6:167–180. 2005. View Article : Google Scholar : PubMed/NCBI

33 

Patel RA, Forinash KD, Pireddu R, Sun Y, Sun N, Martin MP, Schönbrunn E, Lawrence NJ and Sebti SM: RKI-1447 is a potent inhibitor of the Rho-associated ROCK kinases with anti-invasive and antitumor activities in breast cancer. Cancer Res. 72:5025–5034. 2012. View Article : Google Scholar : PubMed/NCBI

34 

Whatcott CJ, Ng S, Barrett MT, Hostetter G, Von Hoff DD and Han H: Inhibition of ROCK1 kinase modulates both tumor cells and stromal fibroblasts in pancreatic cancer. PLoS One. 12:e01838712017. View Article : Google Scholar : PubMed/NCBI

35 

Wang X, Huang Y, Guo R and Liu Y, Qian Y, Liu D, Dai X, Wei Z, Jin F and Liu Y: Clinicopathological significance of ROCK1 and PIK3CA expression in nasopharyngeal carcinoma. Exp Ther Med. 13:1064–1068. 2017. View Article : Google Scholar : PubMed/NCBI

36 

Wu D, Niu X, Pan H, Zhou Y, Qu P and Zhou J: MicroRNA-335 is downregulated in bladder cancer and inhibits cell growth, migration and invasion via targeting ROCK1. Mol Med Rep. 13:4379–4385. 2016. View Article : Google Scholar : PubMed/NCBI

37 

Zhang S, Zhao Y and Wang L: MicroRNA-198 inhibited tumorous behaviors of human osteosarcoma through directly targeting ROCK1. Biochem Biophys Res Commun. 472:557–565. 2016. View Article : Google Scholar : PubMed/NCBI

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October 2019
Volume 20 Issue 4

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APA
Wang, L., Wang, L., Li, L., Zhang, H., & Lyu, X. (2019). MicroRNA‑330 is downregulated in retinoblastoma and suppresses cell viability and invasion by directly targeting ROCK1. Molecular Medicine Reports, 20, 3440-3447. https://doi.org/10.3892/mmr.2019.10545
MLA
Wang, L., Wang, L., Li, L., Zhang, H., Lyu, X."MicroRNA‑330 is downregulated in retinoblastoma and suppresses cell viability and invasion by directly targeting ROCK1". Molecular Medicine Reports 20.4 (2019): 3440-3447.
Chicago
Wang, L., Wang, L., Li, L., Zhang, H., Lyu, X."MicroRNA‑330 is downregulated in retinoblastoma and suppresses cell viability and invasion by directly targeting ROCK1". Molecular Medicine Reports 20, no. 4 (2019): 3440-3447. https://doi.org/10.3892/mmr.2019.10545