Knockdown of SP1/Syncytin1 axis inhibits the proliferation and metastasis through the AKT and ERK1/2 signaling pathways in non‐small cell lung cancer

Abstract

Syncytin 1 is considered as an oncogene in various malignant tumors, but its effect on non‐small cell lung cancer (NSCLC) has not been reported. We investigated the specific role of Syncytin 1 on NSCLC through the transfection of Syncytin 1 knockdown or overexpression plamids in A549 cells. Our results proved that knockdown of Syncytin 1 inhibited the proliferation, and blocked the cell cycle on G1 phase by inhibiting the expression of Nusap1, Cyclin D1, CDK6, and CDK4. Cell cycle arrest also leaded to increased apoptosis in Syncytin 1 knockdown cells. Suppression of Syncytin 1 inhibited the migration and invasion, as well as the expressions of epithelial‐mesenchymal transition (EMT) makers, N‐cadherin, β‐catenin, and Vimentin, indicating that Syncytin 1 knockdown inhibited the metastasis via reversing the EMT process in A549 cells. The phosphorylation levels of Akt, mTOR, and Erk1/2 were all decreased in Syncytin 1 knockdown cells, suggesting the signaling pathways by which Syncytin 1 operated as an oncogene in NSCLC. Moreover, the underexpression of transcription factor SP1 downregulated the Syncytin 1 expression in A549 cells. The rescue experiment of Syncytin 1 in SP1 knockdown cells further proved that Syncytin 1 could block the inhibition of cell growth induced by SP1 knockdown. In conclusion, knockdown of SP1/Syncytin1 axis inhibited the progression of NSCLC by the reversion of tumor epithelial‐mesenchymal transition process and suppression of Akt and Erk signaling pathways, suggesting that they are potential targets for targeted therapy of NSCLC.

<p>Long Non-Coding RNA LINC00491 Contributes to the Malignancy of Non-Small-Cell Lung Cancer via Competitively Binding to microRNA-324-5p and Thereby Increasing Specificity Protein 1 Expression</p>

“…SP1 was reported to be expressed at high levels in NSCLC and involved in NSCLC progression by regulating multiple aggressive behaviors. [28][29][30] Our rescue experiments further demonstrated that the miR-324-5p inhibition or SP1 overexpression partially reversed the tumorinhibiting impacts of LINC00491 knockdown in NSCLC cells. These results suggested that the miR-324-5p/SP1 axis was required for LINC00491-triggered regulatory mechanism in the malignancy of NSCLC.…”

“…Among them, SP1 (Figure 4A) was chosen for further corroboration due to its wellcharacterized pro-oncogenic roles during NSCLC progression. [28][29][30] Luciferase reporter assay was employed to verify the predicted results. The results revealed that ectopic miR-324-5p expression reduced the luciferase activity driven by the SP1-WT in H522 and SK-MES-1 cells, while it did not affect the luciferase activity of SP1-MUT (Figure 4B).…”

RNA binding proteins involved in regulation of protein synthesis to initiate biogenesis of secondary tumor in hepatocellular carcinoma in mice

“…They also might constitute spliceosome to abnormally participate in the splicing of mRNA, regulation of genes expression, causing abnormalities in protein synthesis. Other examples were the binding of miRNA or piRNA to cause the degradation of relevant RNA and result in functional disorder of their target molecules downstream of the ncRNA (Viswanathan, Daley & Gregory, 2008;Dong et al, 2019;Li et al, 2019d). They could also bind the mRNA or ribonucleoproteins to block or promote the translation of proteins (Seetharaman et al, 2016;Fei et al, 2017).…”

Identify key genes and pathways in pancreatic ductal adenocarcinoma via bioinformatics analysis

“…In non-small cell lung cancer, the inhibited expression of NUSAP1 could result in the blocking the cell cycle on G1 phase. 28 . In addition, NUSAP1 Inhibited Cell Proliferation in Invasive Breast Cancer Cells.…”