Long non‑coding RNA TP73 antisense RNA 1 facilitates the proliferation and migration of cervical cancer cells via regulating microRNA‑607/cyclin D2

Zhang,Hongmei; Xue,Bing; Wang,Shuyuan; Li,Xiaoxia; Fan,Tingting

doi:10.3892/mmr.2019.10572

Long non‑coding RNA TP73 antisense RNA 1 facilitates the proliferation and migration of cervical cancer cells via regulating microRNA‑607/cyclin D2

Authors:
- Hongmei Zhang
- Bing Xue
- Shuyuan Wang
- Xiaoxia Li
- Tingting Fan
View Affiliations

Affiliations: Department of Pathology, Jining No. 1 People's Hospital, Jining, Shandong 272011, P.R. China, Department of Pathology, Affiliated Hospital of Jining Medical University, Jining, Shandong 272000, P.R. China , Department of Gynecology, Tai'an Tumour Prevention and Treatment Hospital, Tai'an, Shandong 271000, P.R. China , Department of Gynecology, People's Hospital of Chongqing Hechuan, Chongqing 401519, P.R. China
Published online on: August 8, 2019 https://doi.org/10.3892/mmr.2019.10572
Pages: 3371-3378

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

The present study aimed to explore the effect of the long non‑coding RNA TP73 antisense RNA 1 (TP73‑AS1) on cervical cancer progression. Cervical cancer and adjacent tissues were collected from 56 patients and assessed. In addition, HeLa and CaSki cells were transfected with various plasmids, inhibitors and corresponding controls, and then Cell Counting Kit‑8 and Transwell assays were used to detect the cell proliferation, migration and invasion abilities. Luciferase reporter gene assay was also performed in HeLa cells. Reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR) was used to investigate TP73‑AS1, microRNA‑607 (miR‑607) and cyclin D2 (CCND2) gene expression, while CCND2 protein expression was determined by western blot analysis. The results revealed that the TP73‑AS1 level was upregulated in cervical cancer tissues (P<0.05) and predicted a poor 5‑year overall survival (P<0.05). HeLa and CaSki cells transfected with siTP73‑AS1 exhibited reduced proliferation, migration and invasion abilities when compared with those in the siNC group (P<0.05). Furthermore, miR‑607 was found to be negatively regulated by TP73‑AS1, while CCND2 was negatively regulated by miR‑607. HeLa and CaSki cells transfected with siTP73‑AS1 exhibited lower CCND2 mRNA and protein expression levels compared with the siNC and siTP73‑AS1 + miR‑inhibitor groups (P<0.05). Compared with the siNC and siTP73‑AS1 + CCND2 overexpression groups, siTP73‑AS1‑transfected HeLa and CaSki cells had decreased proliferation, migration and invasion abilities (P<0.05). In conclusion, the findings suggested that upregulation of TP73‑AS1 promoted cervical cancer progression by promoting CCND2 via the suppression of miR‑607 expression.

View Figures

View References

1	Ferlay J, Soerjomataram I, Dikshit R, Eser S, Mathers C, Rebelo M, Parkin DM, Forman D and Bray F: Cancer incidence and mortality worldwide: Sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer. 136:E359–E386. 2015. View Article : Google Scholar : PubMed/NCBI
2	Jemal A, Bray F, Center MM, Ferlay J, Ward E and Forman D: Global cancer statistics. CA Cancer J Clin. 61:69–90. 2011. View Article : Google Scholar : PubMed/NCBI
3	de Freitas AC, Gomes Leitão Mda C and Coimbra EC: Prospects of molecularly-targeted therapies for cervical cancer treatment. Curr Drug Targets. 16:77–91. 2015. View Article : Google Scholar : PubMed/NCBI
4	Yang Q, Huang H, Gong Z, Xiong W, Zeng Z and Li G: Advances in regulation of gene expression mediated by lncRNAs. Zhong Nan Da Xue Xue Bao Yi Xue Ban. 39:91–95. 2014.(In Chinese). PubMed/NCBI
5	Liu W, Ma R and Yuan Y: Post-transcriptional regulation of genes related to biological behaviors of gastric cancer by long noncoding RNAs and MicroRNAs. J Cancer. 8:4141–4154. 2017. View Article : Google Scholar : PubMed/NCBI
6	Zhao Y, Huang J, Liu T, He S, Shang C, Guo L, Du Q and Yao S: Overexpression of long non-coding RNA RP11-396F22.1 correlates poor prognosis of patients with early-stage cervical cancer. Am J Transl Res. 10:684–695. 2018.PubMed/NCBI
7	Liu Y, Yang Y, Li L, Liu Y, Geng P, Li G and Song H: lncRNA SNHG1 enhances cell proliferation, migration, and invasion in cervical cancer. Biochem Cell Biol. 96:38–43. 2018. View Article : Google Scholar : PubMed/NCBI
8	Wu X, Cao X and Chen F: WITHDRAWN: lncRNA-HOTAIR activates tumor cell proliferation and migration by suppressing MiR-326 in cervical cancer. Oncol Res. Aug 31–2017.(Epub ahead of print). View Article : Google Scholar :
9	Cao S, Liu W, Li F, Zhao W and Qin C: Decreased expression of lncRNA GAS5 predicts a poor prognosis in cervical cancer. Int J Clin Exp Pathol. 7:6776–6783. 2014.PubMed/NCBI
10	Zhu FY, Chen MX, Ye NH, Shi L, Ma KL, Yang JF, Cao YY, Zhang Y, Yoshida T, Fernie AR, et al: Proteogenomic analysis reveals alternative splicing and translation as part of the abscisic acid response in Arabidopsis seedlings. Plant J. 91:518–533. 2017. View Article : Google Scholar : PubMed/NCBI
11	Zhang R, Jin H and Lou F: The long non-coding RNA TP73-AS1 interacted with miR-142 to modulate brain glioma growth through HMGB1/RAGE pathway. J Cell Biochem. 119:3007–3016. 2018. View Article : Google Scholar : PubMed/NCBI
12	Zou Q, Zhou E, Xu F, Zhang D, Yi W and Yao J: A TP73-AS1/miR-200a/ZEB1 regulating loop promotes breast cancer cell invasion and migration. J Cell Biochem. 119:2189–2199. 2018. View Article : Google Scholar : PubMed/NCBI
13	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
14	Xia L, Wu L, Bao J, Li Q, Chen X, Xia H and Xia R: Circular RNA circ-CBFB promotes proliferation and inhibits apoptosis in chronic lymphocytic leukemia through regulating miR-607/FZD3/Wnt/β-catenin pathway. Biochem Biophys Res Commun. 503:385–390. 2018. View Article : Google Scholar : PubMed/NCBI
15	Du X, Lin LI, Zhang L and Jiang J: microRNA-195 inhibits the proliferation, migration and invasion of cervical cancer cells via the inhibition of CCND2 and MYB expression. Oncol Lett. 10:2639–2643. 2015. View Article : Google Scholar : PubMed/NCBI
16	Zhao XL, Zhao ZH, Xu WC, Hou JQ and Du XY: Increased expression of SPRY4-IT1 predicts poor prognosis and promotes tumor growth and metastasis in bladder cancer. Int J Clin Exp Pathol. 8:1954–1960. 2015.PubMed/NCBI
17	Li X, Wang X, Mao L, Zhao S and Wei H: lncRNA TP73-AS1 predicts poor prognosis and promotes cell proliferation in ovarian cancer via cell cycle and apoptosis regulation. Mol Med Rep. 18:516–522. 2018.PubMed/NCBI
18	Fan X, Chen W, Fu Z, Zeng L, Yin Y and Yuan H: MicroRNAs, a subpopulation of regulators, are involved in breast cancer progression through regulating breast cancer stem cells. Oncol Lett. 14:5069–5076. 2017.PubMed/NCBI
19	González-Quintana V, Palma-Berré L, Campos-Parra AD, López-Urrutia E, Peralta-Zaragoza O, Vazquez-Romo R and Pérez-Plasencia C: MicroRNAs are involved in cervical cancer development, progression, clinical outcome and improvement treatment response (Review). Oncol Rep. 35:3–12. 2016. View Article : Google Scholar : PubMed/NCBI
20	Su Z, Yang H, Zhao M, Wang Y, Deng G and Chen R: MicroRNA-92a promotes cell proliferation in cervical cancer via inhibiting p21 expression and promoting cell cycle progression. Oncol Res. 25:137–145. 2017. View Article : Google Scholar : PubMed/NCBI
21	Zhang Z, Wang J, Li J, Wang X and Song W: MicroRNA-150 promotes cell proliferation, migration, and invasion of cervical cancer through targeting PDCD4. Biomed Pharmacother. 97:511–517. 2018. View Article : Google Scholar : PubMed/NCBI
22	Zhang Z, Wang J, Wang X, Song W, Shi Y and Zhang L: MicroRNA-21 promotes proliferation, migration, and invasion of cervical cancer through targeting TIMP3. Arch Gynecol Obstet. 297:433–442. 2018. View Article : Google Scholar : PubMed/NCBI
23	Yang YK, Xi WY, Xi RX, Li JY, Li Q and Gao YE: MicroRNA-494 promotes cervical cancer proliferation through the regulation of PTEN. Oncol Rep. 33:2393–2401. 2015. View Article : Google Scholar : PubMed/NCBI
24	Fang H, Shuang D, Yi Z, Sheng H and Liu Y: Up-regulated microRNA-155 expression is associated with poor prognosis in cervical cancer patients. Biomed Pharmacother. 83:64–69. 2016. View Article : Google Scholar : PubMed/NCBI
25	Lin YF, Li LH, Lin CH, Tsou MH, Chuang MT, Wu KM, Liao TL, Li JC, Wang WJ, Tomita A, et al: Selective retention of an inactive allele of the DKK2 tumor suppressor gene in hepatocellular carcinoma. PLoS Genet. 12:e10060512016. View Article : Google Scholar : PubMed/NCBI
26	Wang N, Wei H, Yin D, Lu Y, Zhang Y, Zhang Q, Ma X and Zhang S: MicroRNA-195 inhibits proliferation of cervical cancer cells by targeting cyclin D1a. Tumour Biol. 37:4711–4720. 2016. View Article : Google Scholar : PubMed/NCBI
27	Shi C and Zhang Z: MicroRNA-362 is downregulated in cervical cancer and inhibits cell proliferation, migration and invasion by directly targeting SIX1. Oncol Rep. 37:501–509. 2017. View Article : Google Scholar : PubMed/NCBI
28	Jiang Z, Song Q, Zeng R, Li J, Li J, Lin X, Chen X, Zhang J and Zheng Y: MicroRNA-218 inhibits EMT, migration and invasion by targeting SFMBT1 and DCUN1D1 in cervical cancer. Oncotarget. 7:45622–45636. 2016.PubMed/NCBI
29	Chen CL, Wang Y, Pan QZ, Tang Y, Wang QJ, Pan K, Huang LX, He J, Zhao JJ, Jiang SS, et al: Bromodomain-containing protein 7 (BRD7) as a potential tumor suppressor in hepatocellular carcinoma. Oncotarget. 7:16248–16261. 2016.PubMed/NCBI
30	Sun L, Jiang R, Li J, Wang B, Ma C, Lv Y and Mu N: MicoRNA-425-5p is a potential prognostic biomarker for cervical cancer. Ann Clin Biochem. 54:127–133. 2017. View Article : Google Scholar : PubMed/NCBI
31	Yang Y, Song KL, Chang H and Chen L: Decreased expression of microRNA-126 is associated with poor prognosis in patients with cervical cancer. Diagn Pathol. 9:2202014. View Article : Google Scholar : PubMed/NCBI
32	Deshpande A, Sicinski P and Hinds PW: Cyclins and cdks in development and cancer: A perspective. Oncogene. 24:2909–2915. 2005. View Article : Google Scholar : PubMed/NCBI
33	Ely S, Di Liberto M, Niesvizky R, Baughn LB, Cho HJ, Hatada EN, Knowles DM, Lane J and Chenkiang S: Mutually exclusive cyclin-dependent kinase 4/cyclin D1 and cyclin-dependent kinase 6/cyclin D2 pairing inactivates retinoblastoma protein and promotes cell cycle dysregulation in multiple myeloma. Cancer Res. 65:11345–11353. 2005. View Article : Google Scholar : PubMed/NCBI