LncRNA CCAT1通过TGF-β/Smad信号通路对子宫内膜癌细胞增殖、侵袭和迁移的影响

doi:10.13481/j.1671-587x.20200519

Abstract

Abstract: Objective: To investigate the effects of long-chain non-coding RNA (LncRNA) CCAT1 on the proliferation, invasion, migration and transforming growth factor-β (TGF-β)/Smad signaling pathway of the endometrial cancer cells,and to elucidate the role of CCAT1 in the occurrence and development of endometrial cancer and its possible mechanism. Methods: The human endometrial cancer Ishiwaka cells were divided into blank control group, negative control group, CCAT1-siRNA group and CCAT1-siRNA+LY364947 group.The cells in negative control group were transfected with negative control siRNA,the cells in CCAT1-siRNA group were transfected with CCAT1-siRNA; the cells in CCAT1-siRNA+LY364947 group were transfected with CCAT1-siRNA and added with LY364947 (3μL),and the cells in blank control group were not transfected.RT-PCR method was used to determine the CCAT1 miRNA expression levels.CCK8 method was used to measure proliferation abilities of cells.Transwell chamber experiment was used to measure the abilities of invasion and migration of cells.Western blotting method was used to measure the expression levels of proliferating cell nuclear antigen (PCNA), E-cadherin, vimentin, snail, Twist, Smad2/3, phosphorylated Smad2/3 (p-Smad2/3) and TGF-β1 proteins in the Ishiwaka cells in various groups. Results: The expression level of CCAT1 mRNA in the Ishiwaka cells was very obvious higher than that in the human endometrial matrix T-HESC cells (t=12.929, P<0.01).Compared with blank control group and negative control group,the CCAT1 miRNA expression levels, the proliferation abilities of cells the number of invasion cells and the number migration cells in CCAT1-siRNA group and CCAT1-siRNA+LY36494 group were obviously decreased (P<0.05),the expression levels of PCNA, vimentin, snail, Twist, p-Smad2/3 and TGF-β1 proteins were obviously decreased (P<0.05),and the expression levels of E-cadherin protein were obviously increased (P<0.05). Compared with CCAT1-siRNA group, the proliferation ability of cells, the number of invasion cells and the number of migration cells in CCAT1-siRNA+LY364947 group were obviously decreased (P<0.05),the expression levels of PCNA, vimentin, snail, Twist, p-Smad2/3 and TGF-β1 proteins were obviously decreased (P<0.05),and the expression level of E-cadherin protein was obviously increased (P<0.05).There were no significant differences in the indexes mentioned above in the Ishiwaka cells between blank control group and negative control group (P>0.05). Conclusion: Silencing LncRNA CCAT1 can inhibit the proliferation, invasion and migration of endometrial cancer cells by inhibiting the TGF-β/Smad signaling pathway.

Key words: long non-coding RNA, endometrial cancer, cell proliferation, cell invasion, cell migration, epithelial-mesenchymal transition, transforming growth factor-β/Smad signaling pathway

CLC Number:

R737.33

WEI Xujing, LI Lin, ZHANG Hongzhen, WANG Jing, XU Jing. Effects of LncRNA CCAT1 on proliferation,invasion and migration of endometrial cancer cells through TGF-β1/smad signaling pathway[J].Journal of Jilin University(Medicine Edition), 2020, 46(05): 1016-1022.

References

[1] LI Z, YU Z, MENG X, et al. Long noncoding RNA GAS5 impairs the proliferation and invasion of endometrial carcinoma induced by high glucose via targeting miR-222-3p/p27[J]. Am J Transl Res, 2019, 11(4):2413-2421.
[2] ZHANG Z, XIE H, LIANG D, et al. Long non-coding RNA CCAT1 as a diagnostic and prognostic molecular marker in various cancers:a meta-analysis[J]. Oncotarget, 2018, 9(34):23695-23703.
[3] YU J, JIANG L, GAO Y, et al. LncRNA CCAT1 negatively regulates miR-181a-5p to promote endometrial carcinoma cell proliferation and migration[J]. Exp Ther Med, 2019, 17(5):4259-4266.
[4] SAHOO S S, QUAH M Y, NIELSEN S, et al. Inhibition of extracellular matrix mediated TGF-β signalling suppresses endometrial cancer metastasis[J]. Oncotarget, 2017, 8(42):71400-71417.
[5] 毛晓丹, 谭宇思, 李玉红, 等. 转化生长因子β1作用下绒毛膜癌JEG-3细胞c-myc mRNA表达[J]. 临床和实验医学杂志, 2014, 13(3):168-171.
[6] LIU Y, WANG L L, CHEN S, et al. LncRNA ABHD11-AS1 promotes the development of endometrial carcinoma by targeting cyclin D1[J]. J Cell Mol Med, 2018, 22(8):3955-3964.
[7] SUN M Y, ZHU J Y, ZHANG C Y, et al. Autophagy regulated by lncRNA HOTAIR contributes to the cisplatin-induced resistance in endometrial cancer cells[J]. Biotechnol Lett, 2017, 39(10):1477-1484.
[8] XIE P, CAO H, LI Y, et al. Knockdown of lncRNA CCAT2 inhibits endometrial cancer cells growth and metastasis via sponging miR-216b[J]. Cancer Biomark, 2017, 21(1):123-133.
[9] LU L, QI H, LUO F, et al. Feedback circuitry via let-7c between lncRNA CCAT1 and c-Myc is involved in cigarette smoke extract-induced malignant transformation of HBE cells[J]. Oncotarget, 2017, 8(12):19285-19297.
[10] 王圣坦, 朱根海,洪澜, 等. 长链非编码CCAT1靶向miR-219a对宫颈癌Hela细胞生长、侵袭和迁移的调节作用[J]. 安徽医科大学学报, 2018, 53(9):1348-1353.
[11] ZHANG E, HAN L, YIN D, et al. H3K27 acetylation activated-long non-coding RNA CCAT1 affects cell proliferation and migration by regulating SPRY4 and HOXB13 expression in esophageal squamous cell carcinoma[J]. Nucleic Acids Res, 2017, 45(6):3086-3101.
[12] YU Q, ZHOU X, XIA Q, et al. Long non-coding RNA CCAT1 that can be activated by c-Myc promotes pancreatic cancer cell proliferation and migration[J]. Am J Transl Res, 2016, 8(12):5444-5454.
[13] 潘洪丽, 何宝玉, 韦东, 等. 长链非编码RNA CCAT1对子宫内膜癌细胞迁移侵袭及上皮-间质转化的影响[J]. 实用医学杂志, 2017, 33(4):598-602.
[14] GARCIA-RENDUELES A R, RODRIGUES J S, GARCIA-RENDUELES M E, et al. Rewiring of the apoptotic TGF-β-SMAD/NFκB pathway through an oncogenic function of p27 in human papillary thyroid cancer[J]. Oncogene, 2017, 36(5):652-666.
[15] COLAK S, TEN DIJKE P. Targeting TGF-β signaling in cancer[J]. Trends Cancer, 2017, 3(1):56-71.
[16] Syed V.TGF-β Signaling in Cancer[J]. J Cell Biochem, 2016, 117(6):1279-1287.
[17] 余南荣, 曾祥, 徐厚巍, 等. LncRNA CCAT通过调控MYC蛋白的表达激活MAPK信号通路影响胃癌细胞的生物学行为[J]. 中国免疫学杂志, 2018, 34(9):1298-1303.
[18] LIN H P, CHENG W, YAN H H, et al. Overexpression of the long noncoding RNA CCAT1 promotes metastasis via epithelial to mesenchymal transition in lung adenocarcinoma[J]. Oncol Lett, 2018:1809-1814.
[19] MU Y, LI N, CUI Y L. The lncRNA CCAT1 upregulates TGFβR1 via sponging miR-490-3p to promote TGFβ1-induced EMT of ovarian cancer cells[J]. Cancer Cell Int, 2018, 18:145.
[20] WANG X K, LAI Q H, HE J, et al. LncRNA SNHG6 promotes proliferation, invasion and migration in colorectal cancer cells by activating TGF-β/Smad signaling pathway via targeting UPF₁ and inducing EMT via regulation of ZEB1[J]. Int J Med Sci, 2019, 16(1):51-59.
[21] KOWALSKA E, BARTNICKI F, FUJISAWA R, et al. Inhibition of DNA replication by an anti-PCNA aptamer/PCNA complex[J]. Nucleic Acids Res, 2018, 46(1):25-41.
[22] MENDONSA A M, NA T Y, GUMBINER B M. E-cadherin in contact inhibition and cancer[J]. Oncogene, 2018, 37(35):4769-4780.
[23] ZHAO L, ZHANG P, SU X J, et al. The ubiquitin ligase TRIM56 inhibits ovarian cancer progression by targeting vimentin[J]. J Cell Physiol, 2018, 233(3):2420-2425.
[24] WANG G H, MA W, LI Y, et al. Prognostic value of Twist, Snail and E-cadherin expression in pathological N0 non-small-cell lung cancer:a retrospective cohort study[J]. Eur J Cardiothorac Surg, 2018, 54(2):237-245.
[25] MA J, WANG L, LI J, et al. Swainsonine inhibits invasion and the EMT process in esophageal carcinoma cells by targeting Twist1[J]. Oncol Res, 2018, 26(8):1207-1213.

Effects of LncRNA CCAT1 on proliferation,invasion and migration of endometrial cancer cells through TGF-β1/smad signaling pathway

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