<p>LncRNA PCAT6 Accelerates the Progression and Chemoresistance of Cervical Cancer Through Up-Regulating ZEB1 by Sponging miR-543</p>

Abstract

Background: Cervical cancer (CC) is a common cancer with a poor prognosis due to the chemoresistance of CC cells to cisplatin. This study aimed to investigate the biological significance of lncRNA prostate cancer-associated transcript 6 (PCAT6) in the carcinogenesis of CC. Materials and Methods: Quantitative real-time polymerase chain reaction (qRT-PCR) was carried out to measure the abundance of PCAT6, miR-543 and zinc finger E-box binding protein 1 (ZEB1) in CC tissues and cells. The combination between miR-543 and lncRNA PCAT6 or ZEB1 was predicted by Starbase and was verified by dual-luciferase reporter assay, RNA-pull down assay and RNA immunoprecipitation (RIP) assay. Cell proliferation and chemoresistance to cisplatin were detected by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Cell apoptosis and metastasis were determined by flow cytometry, Western blot and transwell migration and invasion assays. Results: The abundance of ZEB1 protein was measured by Western blot assay. Murine xenograft model was established to confirm the function of lncRNA PCAT6 in vivo. The abundance of lncRNA PCAT6 was enhanced in CC tissues and cells compared with that in corresponding normal tissues and normal cervical epithelial cells Ect1/E6E7. MiR-543 was a target of PCAT6 and was negatively regulated by PCAT6. PCAT6 accelerated the proliferation, metastasis and the chemoresistance of CC cells to cisplatin while suppressed the apoptosis of CC cells. The overexpression of PCAT6 reversed the inhibitory effects of miR-543 accumulation on the proliferation, metastasis and chemoresistance of CC cells to cisplatin and the promoting impact on the apoptosis of CC cells. ZEB1 was a direct target of miR-543, and it functioned as the downstream gene of PCAT6/miR-543 to exert its oncogenic role in CC. PCAT6 promoted the growth of murine xenograft tumor through miR-543/ZEB1 axis in vivo. Conclusion: LncRNA PCAT6 facilitated the proliferation, metastasis and chemoresistance of CC cells to cisplatin while impeded the apoptosis of CC cells via PCAT6/miR-543/ZEB1 axis. PCAT6/miR-543/ZEB1 axis might be a promising target for CC therapy.

RETRACTED ARTICLE: LncRNA PCAT6 regulates the progression of pituitary adenomas by regulating the miR-139-3p/BRD4 axis

“…In view of the close relations between cell proliferation and the regulation of cell cycle distribution, and between apoptosis and the regulation of key factors in apoptosis (Bcl-2, Bax, Cleaved caspase-3) [ 26 – 28 ], we further detected cell cycle distribution and the expressions of the apoptosis-related proteins, and discovered that miR-139-3p mimic and shPCAT6 could induce cell cycle arrest in G0/G1 phase, suppress Bcl-2 expression, and enhance Bax and Cleaved caspase-3 expressions in PA cells. Besides, the previous studies also found that high expression of lncRNA PCAT6 showed a close association with tumor occurrence and development in ovarian cancer as well as the chemoresistance of cervical cancer [ 14 , 15 ]. Our study focused on the regulatory effects of PCAT6 expression on cell biological behaviors in PA. As mentioned above, miR-139-3p inhibitor reversed the effect of shPCAT6 on PA cells.…”

“…For instance, lncRNAs MEG3 and HOTAIR were found associated with the development of non-invasion PA (NIPA) into IPA, as evidence by the decrease in MEG3 level and increase in HOTAIR level during the development transformation of normal pituitary into NIPA and eventually into IPA tissues [ 9 ]; lncRNA H19 was up-regulated in IPA, and thereby could be used as a biomarker for PA diagnosis [ 10 ]; the knockdown of lncRNA AFAP1-AS1 could suppress cell growth and induce apoptosis in PA [ 11 ]; moreover, lncRNA SNHG1 had a high level in IPA and could activate the Wnt/beta-catenin pathway in IPA [ 12 ]. In addition, previous research has also proved that lncRNA PCAT6 was abnormally expressed in different types of cancers such as cervical cancer, liver cancer, and ovarian cancer, and had the ability to modulate the processes of these cancers [ 13 – 15 ]. To our knowledge, however, the level and role of PCAT6 in the development of PA have not been reported.…”

<p>Knockdown of MIR4435-2HG Suppresses the Proliferation, Migration and Invasion of Cervical Cancer Cells via Regulating the miR-128-3p/MSI2 Axis in vitro</p>

“…In the past decade, researchers have determined that lncRNAs act as important regulators in the proliferation, migration and invasion of CC cells. 10,11,26 Song et al have disclosed that down-regulation of OIP5-AS1 inhibits viability and promotes apoptosis in CC cells. 9 Zhu et al have disclosed that silencing of CDKN2B-AS1 suppresses metastasis and promotes apoptosis in CC cells.…”

“…9 LncRNA PCAT6 has been reported to accelerate the progression of CC. 10 LncRNA CAR10 expression is significantly up-regulated in CC tissues, whereas overexpression of CAR10 can promote the proliferation of CC cells. 11 Additionally, the emerging evidences have displayed that lncRNA MIR4435-2HG is correlated with the occurrence and progression of many cancers.…”

The role of miR‐543 in human cancerous and noncancerous diseases

“…Similarly, miR‐543 can also be used as a negative regulator of a disintegrin and metalloproteinase 9 (ADAM9) in gliomas, which not only inhibits cell proliferation, but also induces apoptosis, inhibits invasion and metastasis, and can promote tumor growth in mice (Ji et al, 2017; L. Xu et al, 2017). GBM is included in gliomas; a recent study revealed the correlations between LEF1‐AS1, engrailed homeobox 2 (EN2), and miR‐543 in GBM, mechanically, LEF1‐AS1 is an upstream regulator, which upregulates EN2 by sponging miR‐543, and downregulation of miR‐543 elevated GBM cell malignant behaviors like proliferation and invasion (Ma et al, 2020). In osteosarcoma, miR‐543 acts on protein arginine methyltransferase 9 (PRMT9) and Angiopoietin 2 (Angpt2), then increases the proliferation capacity of cancer cells in vitro and promotes tumor growth in vivo (L. H. Wang et al, 2017; H. Zhang et al, 2017).…”