Background: Epithelial-mesenchymal transition (EMT) plays a key role in promoting invasion and metastasis of tumor cells. SEMA4C can regulate the generation of transforming growth factor-beta 1 (TGF-b1)-induced EMT in cervical cancer. This study investigated the relationship between the regulation of SEMA4C on TGF-b1-induced p38 mitogen-activated protein kinase (MAPK) activation and invasion and metastasis of cervical cancer. Material/Methods: Hela-shSEMA4C cell line was established and the success of transfection was confirmed with fluorescence intensity. Cell experiments were divided into 2 groups. Group 1 was Hela, Hela-shNC, and Hela-shSEMA4C; and Group 2 was Hela, Hela-shNC, Hela-shSEMA4C, Hela+TGF-b1, Hela-shNC+TGF-b1, and Hela-shSEMA4C+TGF-b1. Group 1 was detected for SEMA4C mRNA expression by real-time polymerase chain reaction (RT-PCR), cell viability by Cell Counting Kit-8 (CCK-8), F-actin fluorescence intensity by immunofluorescence, cell migration by scratch test, and cell invasion by invasion test. Group 2 was analyzed for E-cadherin fluorescence intensity by immunofluorescence, human fibronectin (FN) content by enzyme-linked immunosorbent assay (ELISA), and SEMA4C, E-cadherin and p-p38 expressions by Western blot. Results: For Group 1, compared with Hela and Hela-shNC subgroups, the SEMA4C mRNA expression, cell viability, F-actin fluorescence intensity, cell migration and invasion ability in the Hela-shSEMA4C subgroup were significantly decreased (P<0.05). For Group 2, compared with Hela and Hela-shNC subgroups, the E-cadherin expression and fluorescence intensity in the Hela-shSEMA4C subgroup were significantly increased (P<0.01), while the FN content, SEMA4C, and p-p38 MAPK expressions were significantly decreased (P<0.01). Compared with Hela-shNC+TGF-b1 and Hela+TGF-b1 subgroups, the E-cadherin expression and fluorescence intensity in the Hela-shSEMA4C+TGF-b1 subgroup were significantly increased (P<0.01), while the FN content, SEMA4C and p-p38 expressions were significantly decreased (P<0.01). Conclusions: Downregulation of SEMA4C can inhibit EMT and the invasion and metastasis of cervical cancer cells via inhibiting TGF-b1-induced Hela cells p38 MAPK activation.

BackgroundMyometrial invasion (MI), lymphovascular space invasion (LVSI), and lymph node metastasis (LNM) have been found to have independent prognostic factors in endometrial cancer. Tumor size has practical advantages in endometrial cancer. The cutoff values for tumor size conformed with current literature. More and more studies inferred that tumor size &gt;20 mm showed a strong correlation. However, the relationship between tumor size &gt;20 mm and MI, LVSI, LNM, recurrence, and overall survival (OS) remains controversial, and no meta-analysis has been conducted. Therefore, a systematic review and meta-analysis should be performed to discuss this issue later on.MethodsRelevant articles were collected from PubMed, EMBASE, and Cochrane Library databases from January 1990 to June 2021. The predictive value of tumor size &gt;20 mm in endometrial cancer was studied, and data were pooled for meta-analysis using Review Manager 5.1. Additionally, the odds ratio (OR) was analyzed, and cumulative analyses of hazard ratio (HR) and their corresponding 95% CI were conducted.ResultsA total of 40 articles with 53,276 endometrial cancer patients were included in the meta-analysis. It contained 7 articles for MI, 6 for LVSI, 21 for LNM, 7 for recurrence, and 3 for OS. Primary tumor size &gt;20 mm was significantly associated with depth of MI (OR = 5.59, 95% CI [5.02, 6.23], p &lt; 0.001), positive LVSI (OR = 3.35, 95% CI [2.34, 4.78], p &lt; 0.001), positive LNM (OR = 4.11, 95% CI [3.63, 4.66], p &lt; 0.001), and recurrence (OR = 3.52, 95% CI [2.39, 5.19], p &lt; 0.001). Tumor size &gt;20 mm was also related to OS via meta-synthesis of HR in univariate survival (HR 2.13, 95% CI [1.28, 3.53], p = 0.003). There was no significant publication bias in this study by funnel plot analysis.ConclusionPrimary tumor size &gt;20 mm was an independent predictive factor for the depth of MI, positive LVSI, positive LNM, recurrence, and poor OS. Therefore, it is more important to take into account the value of tumor size in the clinicopathological staging of endometrial carcinoma. Tumor size &gt;20 mm should be integrated into the intraoperative algorithm for performing a full surgical staging. Well-designed and multicenter studies, with a larger sample size, are still required to verify the findings.