The purpose of this study was to develop an lncRNA signature to improve the prediction of the prognosis of cervical cancer through integration bioinformatics and analysis of TCGA RNA sequencing data. In this study, we established a set of four lncRNA signatures that was significantly associated with recurrence-free survival using the Cox regression model. Functionally, we screened the CC-associated lncRNA NCK1-AS1 as a new candidate lncRNA and regulator which promotes development and progression in CC. qRT-PCR and RNA in situ hybridization (RISH) results showed that NCK1-AS1 was significantly up-regulated in 77.4% (24/31) of the CC tissue group compared with the normal group (P < 0.01). Interestingly, we demonstrated that transcription factor SP1 directly binds to the promoter to activate NCK1-AS1 expression in SiHa cells. In vitro and in vivo assays of silencing NCK1-AS1 significantly inhibited cell proliferation and invasion, with induction of cell arrest in S phase of the cell cycle. Furthermore, Human Transcriptome Array 2.0 analysis after NCK1-AS1 silencing highlighted alterations in cell proliferation and cell cycle pathways. NCK1-AS1 functioned as a molecular sponge for miR-6857, antagonizing its ability to repress CDK1/6 protein translation. In conclusion, these findings suggest that NCK1-AS1/miR-6857/CDK1 crosstalk serve as a critical effector in cervical cancer progression and may serve as a potential target in cervical cancer.
IntroductionCervical cancer, one of the most common malignant gynecological tumors, is a significant burden on the health of females worldwide. The purpose of this study was to investigate genes associated with lymph node metastasis in cervical cancer.MethodsWe report on the lymph node metastasis-associated gene, small cell adhesion glycoprotein (SMAGP), as a key regulator of cervical cancer development and progression. SMAGP expression levels were investigated in 70 cervical squamous cell carcinoma samples and 10 normal cervical squamous epithelium samples.ResultsImmunohistochemistry analysis revealed that SMAGP protein levels were significantly elevated in cervical cancer tissue compared with normal cervical squamous epithelium. Silencing of SMAGP induced cell cycle arrest, inhibited the cell proliferation and colony formation ability of cervical cancer cells in vitro and suppressed their tumorigenic potential in nude mice. In addition, SMAGP knockdown reduced expression of epithelial mesenchymal transition-related proteins, including vimentin, β-cadherin, MMP2, and Twist.ConclusionTogether, our findings demonstrate that SMAGP plays a critical role in cell proliferation and tumorigenesis and could be a new therapeutic target in cervical cancer.
On page 6933, Figure 4B artwork is incorrect. Figure 4B artwork was mistakenly interchanged by the Editorial staff during the publication process. The correct Figure 4 is as follows: Figure 4 SMAGP down-regulation inhibited the migration and invasion ability of cervical cancer cells. Notes: (A, B) SMAGP was knocked down with siRNA(siNCand si581) and lentivirus (shNC, shSMAGP). Knockdown of SMAGP inhibited CaSki cell migration and invasion. (C) Knockdown of SMAGP inhibits CaSki metastasis in nude mice. CaSki cells stably expressing shSMAGP were injected into nude mice twice per week. At 28 days after injection, the tumor mass and related tissues were removed. In the NCgroup, many tumors were found around the intestine; however, tumors only developed at the injection site in the experimental group. Ascites extracted from the NC group exhibited green fluorescence.
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