FOXD3‑AS1/miR‑128‑3p/LIMK1 axis regulates cervical cancer progression

Yang,Xiufang; Du,Huilan; Bian,Wenhui; Li,Qingxue; Sun,Hairu

doi:10.3892/or.2021.8013

FOXD3‑AS1/miR‑128‑3p/LIMK1 axis regulates cervical cancer progression

Authors:
- Xiufang Yang
- Huilan Du
- Wenhui Bian
- Qingxue Li
- Hairu Sun
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Affiliations: Department of Gynecology, Hengshui People's Hospital, Hengshui, Hebei 053000, P.R. China, Department of Gynecology, Hebei University of Chinese Medicine, Shijiazhuang, Hebei 050000, P.R. China, Department of Gynecology, Chinese Medicine Hospital of Hebei, Shijiazhuang, Hebei 050000, P.R. China, Department of Gynecology, The Fourth Hospital of Shijiazhuang, Shijiazhuang, Hebei 050000, P.R. China
Published online on: March 16, 2021 https://doi.org/10.3892/or.2021.8013
Article Number: 62
Copyright: © Yang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Long non‑coding RNA forkhead box D3 antisense RNA 1 (FOXD3‑AS1) functions as an oncogenic regulator in several types of cancer, including breast cancer, glioma and cervical cancer. However, the effects and mechanisms underlying FOXD3‑AS1 in cervical cancer (CC) are not completely understood. The present study aimed to investigate the biological functions and potential molecular mechanisms underlying FOXD3‑AS1 in CC progression. Reverse transcription‑quantitative PCR was performed to detect FOXD3‑AS1, microRNA (miR)‑128‑3p and LIM domain kinase 1 (LIMK1) expression levels in CC tissues and cells. Immunohistochemical staining and western blotting were conducted to assess LIMK1 protein expression levels in CC tissues and cells, respectively. Cell Counting Kit‑8 and BrdU assays were used to determine the role of FOXD3‑AS1 in regulating cell proliferation. CC cell migration and invasion were assessed by performing Transwell assays. Dual‑luciferase reporter assays were conducted to verify the binding between miR‑128‑3p and FOXD3‑AS1. FOXD3‑AS1 expression was significantly increased in CC tissues and cell lines compared with adjacent healthy tissues and normal cervical epithelial cells, respectively. High FOXD3‑AS1 expression was significantly associated with poor differentiation of tumor tissues, increased tumor size and positive lymph node metastasis. FOXD3‑AS1 overexpression significantly increased CC cell proliferation, migration and invasion compared with the negative control (NC) group, whereas FOXD3‑AS1 knockdown resulted in the opposite effects compared with the small interfering RNA‑NC group. Moreover, the results demonstrated that FOXD3‑AS1 targeted and negatively regulated miR‑128‑3p, which indirectly upregulated LIMK1 expression. Therefore, the present study demonstrated that FOXD3‑AS1 upregulated LIMK1 expression via competitively sponging miR‑128‑3p in CC cells, promoting CC progression.

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1	Siegel RL, Miller KD and Jemal A: Cancer Statistics, 2017. CA Cancer J Clin. 67:7–30. 2017. View Article : Google Scholar : PubMed/NCBI
2	Maździarz A, Wyględowski J, Osuch B, Jagielska B and Śpiewankiewicz B: New directions in cervical cancer prophylaxis worldwide and in Poland-Case study of the polish rural female population. Ann Agric Environ Med. 24:592–595. 2017. View Article : Google Scholar : PubMed/NCBI
3	Small W Jr, Bacon MA, Bajaj A, Chuang LT, Fisher BJ, Harkenrider MM, Jhingran A, Kitchener HC, Mileshkin LR, Viswanathan AN and Gaffney DK: Cervical cancer: A global health crisis. Cancer. 123:2404–2412. 2017. View Article : Google Scholar : PubMed/NCBI
4	Chen J, Yu Y, Li H, Hu Q, Chen X, He Y, Xue C, Ren F, Ren Z, Li J, et al: Long non-coding RNA PVT1 promotes tumor progression by regulating the miR-143/HK2 axis in gallbladder cancer. Mol Cancer. 18:332019. View Article : Google Scholar : PubMed/NCBI
5	Zhou C, Zhao J, Liu J, Wei S, Xia Y, Xia W, Bi Y, Yan Z and Huang H: LncRNA SNHG16 promotes epithelial- mesenchymal transition via down-regulation of DKK3 in gastric cancer. Cancer Biomark. 26:393–401. 2019. View Article : Google Scholar : PubMed/NCBI
6	Xu Y, Li J, Wang P, Zhang Z and Wang X: LncRNA HULC promotes lung squamous cell carcinoma by regulating PTPRO via NF-κB. J Cell Biochem. 120:19415–19421. 2019. View Article : Google Scholar : PubMed/NCBI
7	Tong W, Han TC, Wang W and Zhao J: LncRNA CASC11 promotes the development of lung cancer through targeting microRNA-302/CDK1 axis. Eur Rev Med Pharmacol Sci. 23:6539–6547. 2019.PubMed/NCBI
8	Zhao X, Li D, Huang D, Song H, Mei H, Fang E, Wang X, Yang F, Zheng L, Huang K and Tong Q: Risk-associated long noncoding RNA FOXD3-AS1 inhibits neuroblastoma progression by repressing PARP1-mediated activation of CTCF. Mol Ther. 26:755–773. 2018. View Article : Google Scholar : PubMed/NCBI
9	Guan Y, Bhandari A, Xia E, Yang F, Xiang J and Wang O: lncRNA FOXD3-AS1 is associated with clinical progression and regulates cell migration and invasion in breast cancer. Cell Biochem Funct. 37:239–244. 2019. View Article : Google Scholar : PubMed/NCBI
10	Chen ZH, Hu HK, Zhang CR, Lu CY, Bao Y, Cai Z, Zou YX, Hu GH and Jiang L: Down-regulation of long non-coding RNA FOXD3 antisense RNA 1 (FOXD3-AS1) inhibits cell proliferation, migration, and invasion in malignant glioma cells. Am J Transl Res. 8:4106–4119. 2016.PubMed/NCBI
11	Benz F, Roy S, Trautwein C, Roderburg C and Luedde T: Circulating MicroRNAs as biomarkers for sepsis. Int J Mol Sci. 17:782016. View Article : Google Scholar
12	Zhou Y, Wang B, Wang Y, Chen G, Lian Q and Wang H: miR-140-3p inhibits breast cancer proliferation and migration by directly regulating the expression of tripartite motif 28. Oncol Lett. 17:3835–3841. 2019.PubMed/NCBI
13	Zhu X, Ma SP, Yang D, Liu Y, Wang YP, Lin T, Li YX, Yang SH, Zhang WC and Wang XL: miR-142-3p suppresses cell growth by targeting CDK4 in colorectal cancer. Cell Physiol Biochem. 51:1969–1981. 2018. View Article : Google Scholar : PubMed/NCBI
14	Zhou Q, Dong J, Luo R, Zhou X, Wang J and Chen F: MicroRNA-20a regulates cell proliferation, apoptosis and autophagy by targeting thrombospondin 2 in cervical cancer. Eur J Pharmacol. 844:102–109. 2019. View Article : Google Scholar : PubMed/NCBI
15	Wen F, Xu JZ and Wang XR: Increased expression of miR-15b is associated with clinicopathological features and poor prognosis in cervical carcinoma. Arch Gynecol Obstet. 295:743–749. 2017. View Article : Google Scholar : PubMed/NCBI
16	Liang H, Luo R, Chen X, Zhao Y and Tan A: miR-187 inhibits the growth of cervical cancer cells by targeting FGF9. Oncol Rep. 38:1977–1984. 2017. View Article : Google Scholar : PubMed/NCBI
17	Juan C, Hua Q, Ruping Z and Tingting W: miRNA-489 as a biomarker in diagnosis and treatment of cervical cancer. Bratisl Lek Listy. 119:278–283. 2018.PubMed/NCBI
18	Wang R, Liu L, Jiao J and Gao D: Knockdown of MIR4435-2HG suppresses the proliferation, migration and invasion of cervical cancer cells via regulating the miR-128-3p/MSI2 axis in vitro. Cancer Manag Res. 12:8745–8756. 2020. View Article : Google Scholar : PubMed/NCBI
19	Scott RW and Olson MF: LIM kinases: Function, regulation and association with human disease. J Mol Med (Berl). 85:555–568. 2007. View Article : Google Scholar : PubMed/NCBI
20	Zhou Y, Ji J, Hong F, Zhuang J and Wang L: Maternal exposure to nanoparticulate titanium dioxide causes inhibition of hippocampal development involving dysfunction of the Rho/NMDAR signaling pathway in offspring. J Biomed Nanotechnol. 15:839–847. 2019. View Article : Google Scholar : PubMed/NCBI
21	Gong H, Zhou L, Khelfat L, Qiu G, Wang Y, Mao K and Chen W: Rho-associated protein kinase (ROCK) promotes proliferation and migration of PC-3 and DU145 prostate cancer cells by targeting LIM Kinase 1 (LIMK1) and matrix Metalloproteinase-2 (MMP-2). Med Sci Monit. 25:3090–3099. 2019. View Article : Google Scholar : PubMed/NCBI
22	Fu J, Yu J, Chen J, Xu H, Luo Y and Lu H: In vitro inhibitory properties of sesquiterpenes from Chloranthus serratus on cell motility via down-regulation of LIMK1 activation in human breast cancer. Phytomedicine. 49:23–31. 2018. View Article : Google Scholar : PubMed/NCBI
23	Zhang Y, Li A, Shi J, Fang Y, Gu C, Cai J, Lin C, Zhao L and Liu S: Imbalanced LIMK1 and LIMK2 expression leads to human colorectal cancer progression and metastasis via promoting β-catenin nuclear translocation. Cell Death Dis. 9:7492018. View Article : Google Scholar : PubMed/NCBI
24	Chhavi, Saxena M, Singh S, Negi MP, Srivastava AK, Trivedi R, Singh U, Pant MC and Bhatt ML: Expression profiling of G2/M phase regulatory proteins in normal, premalignant and malignant uterine cervix and their correlation with survival of patients. J Cancer Res Ther. 6:167–171. 2010. View Article : Google Scholar : PubMed/NCBI
25	Pfaffl MW: A new mathematical model for relative quantification in real-time RT-PCR. Nucleic Acids Res. 29:e452001. View Article : Google Scholar : PubMed/NCBI
26	Liu S, Zhang W, Liu K and Liu Y: LncRNA SNHG16 promotes tumor growth of pancreatic cancer by targeting miR-218-5p. Biomed Pharmacother. 114:1088622019. View Article : Google Scholar : PubMed/NCBI
27	Zhao J, Li D and Fang L: miR-128-3p suppresses breast cancer cellular progression via targeting LIMK1. Biomed Pharmacother. 115:1089472019. View Article : Google Scholar : PubMed/NCBI
28	Ding X, Jia X, Wang C, Xu J, Gao SJ and Lu C: A DHX9-lncRNA-MDM2 interaction regulates cell invasion and angiogenesis of cervical cancer. Cell Death Differ. 26:1750–1765. 2019. View Article : Google Scholar : PubMed/NCBI
29	Jiang H, Liang M, Jiang Y, Zhang T, Mo K, Su S, Wang A, Zhu Y, Huang G and Zhou R: The lncRNA TDRG1 promotes cell proliferation, migration and invasion by targeting miR-326 to regulate MAPK1 expression in cervical cancer. Cancer Cell Int. 19:1522019. View Article : Google Scholar : PubMed/NCBI
30	Feng S, Liu W, Bai X, Pan W, Jia Z, Zhang S, Zhu Y and Tan W: LncRNA-CTS promotes metastasis and epithelial-to-mesenchymal transition through regulating miR-505/ZEB2 axis in cervical cancer. Cancer Lett. 465:105–117. 2019. View Article : Google Scholar : PubMed/NCBI
31	Ma S, Deng X, Yang Y, Zhang Q, Zhou T and Liu Z: The lncRNA LINC00675 regulates cell proliferation, migration, and invasion by affecting Wnt/β-catenin signaling in cervical cancer. Biomed Pharmacother. 108:1686–1693. 2018. View Article : Google Scholar : PubMed/NCBI
32	Liu Z, Li W, Pang Y, Zhou Z and Liu S, Cheng K, Qin Q, Jia Y and Liu S: SF3B4 is regulated by microRNA-133b and promotes cell proliferation and metastasis in hepatocellular carcinoma. EBioMedicine. 38:57–68. 2018. View Article : Google Scholar : PubMed/NCBI
33	Liu C, Jian M, Qi H and Mao WZ: MicroRNA 495 inhibits proliferation and metastasis and promotes apoptosis by targeting Twist1 in gastric cancer cells. Oncol Res. 27:389–397. 2019. View Article : Google Scholar : PubMed/NCBI
34	Huo L, Wang B, Zheng M, Zhang Y, Xu J, Yang G and Guan Q: miR-128-3p inhibits glioma cell proliferation and differentiation by targeting NPTX1 through IRS-1/PI3K/AKT signaling pathway. Exp Ther Med. 17:2921–2930. 2019.PubMed/NCBI
35	Frixa T, Sacconi A, Cioce M, Roscilli G, Ferrara FF, Aurisicchio L, Pulito C, Telera S, Carosi M, Muti P, et al: MicroRNA-128-3p-mediated depletion of Drosha promotes lung cancer cell migration. Carcinogenesis. 39:293–304. 2018. View Article : Google Scholar : PubMed/NCBI
36	Huang CY, Huang XP, Zhu JY, Chen ZG, Li XJ, Zhang XH, Huang S, He JB, Lian F, Zhao YN and Wu GB: miR-128-3p suppresses hepatocellular carcinoma proliferation by regulating PIK3R1 and is correlated with the prognosis of HCC patients. Oncol Rep. 33:2889–2898. 2015. View Article : Google Scholar : PubMed/NCBI
37	Liu Y, Lin X, Zhou S, Zhang P, Shao G and Yang Z: Long noncoding RNA HOXA-AS2 promotes non-small cell lung cancer progression by regulating miR-520a-3p. Biosci Rep. 39:BSR201902832019. View Article : Google Scholar : PubMed/NCBI
38	Huang T, Wang X, Yang X, Ji J, Wang Q, Yue X and Dong Z: Long non-coding RNA DUXAP8 enhances renal cell carcinoma progression via downregulating miR-126. Med Sci Monit. 24:7340–7347. 2018. View Article : Google Scholar : PubMed/NCBI
39	Chen P, Zeng M, Zhao Y and Fang X: Upregulation of Limk1 caused by microRNA-138 loss aggravates the metastasis of ovarian cancer by activation of Limk1/cofilin signaling. Oncol Rep. 32:2070–2076. 2014. View Article : Google Scholar : PubMed/NCBI
40	Liao Q, Li R, Zhou R, Pan Z, Xu L, Ding Y and Zhao L: LIM kinase 1 interacts with myosin-9 and alpha-actinin-4 and promotes colorectal cancer progression. Br J Cancer. 117:563–571. 2017. View Article : Google Scholar : PubMed/NCBI
41	Mardilovich K, Gabrielsen M, McGarry L, Orange C, Patel R, Shanks E, Edwards J and Olson MF: Elevated LIM kinase 1 in nonmetastatic prostate cancer reflects its role in facilitating androgen receptor nuclear translocation. Mol Cancer Ther. 14:246–258. 2015. View Article : Google Scholar : PubMed/NCBI