Comprehensive Analysis of Differential Gene Expression Profile via RNA Sequencing in the Human Ovarian Cancer SKOV3 Cells Treated with Simvastatin

Abstract

The experimental studies have demonstrated that some statins have an anticancer effect against ovarian cancer in vitro and in vivo, however, the potential molecular mechanism is still unclear. In the present study, high throughput RNA sequencing(RNA-seq) technology was applied to exploring the mRNA changes treated with Simvastatin in the human ovarian cancer SKOV3 cell line. The result of CCK-8 assay shows that Simvastatin inhibits significantly SKOV3 cell viability in a concentration-dependent manner, and cell cycle according to the flow cytometry analysis result shows cell cycle arrest of G1 phase is induced in SKOV3 cells with 10 µg/mL simvastatin added for 24 h. The differential expression genes(DEGs) analysis of RNA-seq data shows that there are a total of 372 DEGs found in the Simvastatin group, of which 150 mRNAs are up-regulated and 222 mRNAs are down-regulated(fold change>2.0, q value < 0.05). Real time reverse transcription-polymerase chain reaction(qRT-PCR) experiment has validated that the expression of KLF2, RHOB and CIDEB is up-regulated while that of DKK1, AMOTL2 and ANKRD1 is down-regulated. The DEGs are enriched in thirteen significant KEGG pathways including cell cycle, DNA replication, apoptosis, etc. This study provides supported useful information about transcriptome profiles of SKOV3 cell treated with simvastatin, and offers an application basis for the further researches on the mechanism of Simvastatin in the treatment of ovarian cancer.

Keywords

Simvastatin / Ovarian cancer / RNA sequencing / Gene expression profile

References

[1] Bray F, Ferlay J, Soerjomataram I, Siegel R L, Torre L A, Jemal A. Ca. Cancer. J. Clin., 2018, 68: 394.

[2] Bowtell D D, Böhm S, Ahmed A A, Aspuria P J, Bast R C Jr., Beral V, Berek J S, Birrer M J, Blagden S, Bookman M A, Brenton J, Chiappinelli K B, Martins F C, Coukos G, Drapkin R, Edmondson R, Fotopoulou C, Gabra H, Galon J, Gourley C, Heong V, Huntsman D G, Iwanicki M, Karlan B Y, Kaye A, Lengyel E, Levine D A, Lu KH, McNeish I A, Menon U, Narod S A, Nelson B H, Nephew K P, Pharoah P, Powell D J Jr., Ramos P, Romero I L, Scott C L, Sood A K, Stronach E A, Balkwill F R. Nat. Rev. Cancer, 2015, 15(11): 668.

[3] Weidle U H, Birzele F, Kollmorgen G, Rueger R. Cancer Genom. Proteom., 201, 13(6): 407.

[4] Coleman R L, Brady M F, Herzog T J, Sabbatini P, Armstrong D K, Walker J L, Kim B G, Fujiwara K, Tewari K S, O’Malley D M, Davidson S A, Rubin S C, DiSilvestro P, Basen-Engquist K, Huang H, Chan J K, Spirtos N M, Ashfaq R, Mannel R S. Lancet Oncol., 2017, 18(6): 779.

[5] Schachter M. Fundam. Clin. Pharmacol., 2005, 19(1): 117.

[6] Majidi A, Na R, Jordan S J, De F A, Webb P M. Int. J. Cancer, 2020, 148(7): 1609.

[7] Mohammadian-Hafshejani A, Sherwin C, Heidari-Soureshjani S. J. Prev. Med. Hyg., 2020, 61(3): E331.

[8] Irvin S, Clarke M A, Trabert B, Wentzensen N. Cancer Causes Control, 2020, 31(10): 869.

[9] Harding B N, Delaney J A, Urban R R, Weiss N S. Cancer Epidemiol Biomarkers Prev., 2019, 28(7): 1127.

[10] Rao P S, Rao U S. Mol. Cell Biochem., 2021, 476(2): 743.

[11] Göbel A, Zinna V M, Dell’Endice S, Jaschke N, Kuhlmann J D, Wimberger P, Rachner T D. BMC Cancer, 2020, 20(1): 703.

[12] Kato S, Liberona M F, Cerda-Infante J, Sánchez M, Henríquez J, Bizama C, Bravo M L, Gonzalez P, Gejman R, Brañes J, García K, Ibañez C, Owen G I, Roa J C, Montecinos V, Cuello M A. Endocr. Relat. Cancer, 2018, 25(10): 821.

[13] Jones H M, Fang Z, Sun W, Clark L H, Stine J E, Tran A Q, Sullivan S A, Gilliam T P, Zhou C, Bae-Jump V L. Am. J. Cancer Res., 2017, 7(12): 2478.

[14] Gbelcová H, Rimpelová S, Ruml T, Fenclová M, Kosek V, Hajšlová J, Strnad H, Kolář M, Vítek L. Sci. Rep., 2017, 7: 44219.

[15] Chen C, Wu H, Kong D, Xu Y, Zhang Z, Chen F, Zou L, Li Z, Shui J, Luo H, Liu S H, Yu J, Wang K, Brunicardi F C. Oncol. Rep., 2020, 44(6): 2569.

[16] Vásquez-Bochm L X, Velázquez-Paniagua M, Castro-Vázquez S, Guerrero-Rodríguez S, Mondragon-Peralta A, Fuente-Granada M D L, Pérez-Tapia S M, González-Arenas A, Velasco-Velázquez M. Pharmacol. Rep., 2019, 71(3): 535.

[17] Mahmoud A M, Aboul-Soud M A, Han J, Al-Sheikh Y A, Al-Abd A M, El-Shemy H A. Int. J. Oncol., 201, 48(5): 1886.

[18] Wang G, Cao R, Wang Y Z, Qian G F, Dan H C, Jiang W, Ju L, Wu M, Xiao Y, Wang X H. Sci. Rep., 201, 6: 35783.

[19] Monireh A, Melody V, Seyed N O. J. Cancer Res. Ther., 201, 12(2): 725.

[20] Abba M L, Patil N, Leupold J H, Moniuszko M, Utikal J, Niklinski J, Allgayer H. Cancer Lett., 2017, 387: 84.