Long Non-Coding RNA ZEB1-Antisense 1 Affects Cell Migration and Invasion of Cervical Cancer by Regulating Epithelial-Mesenchymal Transition via the p38MAPK Signaling Pathway

Abstract

Aim: To investigate whether long non-coding RNA (lncRNA) ZEB1 antisense 1 (ZEB1-AS1) affects cell migration and invasion of cervical cancer by regulating epithelial-mesenchymal transition (EMT) via the p38MAPK pathway. Methods: Human cervical cancer cell line Hela was classified into Control, NC siRNA, ZEB1-AS1 siRNA, SB203580 (p38MAPK pathway inhibitor) and ZEB1-AS1 siRNA + Anisomycin (p38MAPK pathway activator) groups. Quantitative real-time polymerase chain reaction was performed for ZEB1-AS1 expression, Western blotting to measure p38MAPK signaling pathway-/EMT-related proteins, and Wound-healing and Transwell assays to evaluate cell migration and invasion respectively. Results: ZEB1-AS1 was upregulated in cancer tissues and related to major clinicopathological features of cervical cancer. Besides, patients with lower-ZEB1-AS1-expression had a higher 5-year survival rate than those patients with higher-ZEB1-AS1-expression. High ZEB1-AS1 expression and advanced Federation of Gynecology and Obstetrics stage were independent risk factors for patients’ prognosis. Both ZEB1-AS1 siRNA and SB203580 effectively reduced p-p38 expression and the migration and invasion of Hela cells, with elevation of E-cadherin and reduction of Vimentin and N-cadherin. However, inhibitory effects of ZEB1-AS1 siRNA on EMT as well as cell migration and invasion of the Hela cell were reversed by Anisomycin. Conclusion: Inhibition of ZEB1-AS1 can block the p38MAPK signaling pathway, ultimately restricting the EMT and suppressing cell migration and invasion of cervical cancer cells.

Prognostic value of long non-coding RNA ZEB1-AS1 in Chinese cancer patients

“…All studies had been carried out in China, and published between 2015 and 2019. Four out of the 21 studies had concentrated on non-small cell lung cancer (NSCLC), [21,23,24,34] 3 on gastric cancer (GC) [22,27,35] and glioma, [28,29,33] 2 on cervical cancer (CVC) [17,19] and colorectal cancer (CRC), [18,20] as well as 1 on hepatocellular carcinoma (HCC), [11] bladder cancer (BC), [25] osteosarcoma (OSC), [26] pancreatic cancer (PC), [10] esophageal squamous cell carcinoma (ESCC), [30] B-lymphoblastic leukemia (B-LL), [31] and Melanoma, [32] respectively. The expression level of lncRNA ZEB1-AS1 had been detected in all tumor specimens.…”

“…[26] Li et al [23] had suggested the regulatory role of lncRNA ZEB1-AS1 in NSCLC, which might potentially serve as a new molecular marker indicating the prognosis as well as the therapeutic target for NSCLC. Gan et al [19] discovered that the down-regulated lncRNA ZEB1-AS1 could block the p38MAPK signaling pathway in the meantime of suppressing CVC cell migration as well as invasion. Liu et al discovered that the down-regulated ZEB1-AS1 would evidently suppress the activity of the Wnt/β-catenin signaling pathway among NSCLC patients.…”

ASF1B promotes cervical cancer progression through stabilization of CDK9

“…Cervical cancer is the fourth leading cause of cancer death in the world and the second most common female malignant tumor, with a mortality rate next only to only that of breast cancer [1][2][3] ; there are~470,000 new cases of CC each year, and the disease poses a great threat to the life of~276,000 females 4 . Among these cases, approximately 90% occur in developing countries, and more than 50,000 females succumb to cervical cancer each year in China 5,6 .…”

<p><em>MiR-139-5p-ZEB1</em> is a Molecular Regulator of Growth, Invasion, and Epithelial-to-Mesenchymal Transition of Cervical Cancer</p>

“…[13][14][15] However, ZEB1 is reported abnormally up-regulated in cases with CC, which affects the proliferation, metastatic behavior, and EMT of CC cells. 16,17 In the present study, we inferred that miR-139-5p-ZEB1 was a molecular regulator of the growth, invasion, and EMT of CC, and thus we conducted relevant studies to verify it.…”