Isoalantolactone induces intrinsic apoptosis through p53 signaling pathway in human lung squamous carcinoma cells

Abstract SASS6 encodes for the Homo sapiens SAS-6 centriolar assembly protein and is important for proper centrosome formation. Although centrosomes are amplified in a wide variety of tumor types, abnormally high SASS6 expression had previously only been identified in colon cancer. Moreover, the role of SASS6 in esophageal squamous cell carcinoma (ESCC) pathogenesis has not yet been elucidated. The aim of this study was to investigate the role and mechanisms of SASS6 in ESCC. In this study, we found that the mRNA and protein levels of SASS6 were increased in human ESCC samples. In addition, SASS6 protein expression was associated with the esophageal cancer stage and negatively affected survival of patients with ESCC. Furthermore, silencing of SASS6 inhibited cell growth and promoted apoptosis of ESCC cells in vitro and inhibited xenograft tumor formation in vivo. A genetic cluster and pathway analysis showed that SASS6 regulated the p53 signaling pathway. Western blot demonstrated that CCND2, GADD45A and EIF4EBP1 protein expression decreased and that TP53 protein expression increased after the knockdown of SASS6 in ESCC cells. Therefore, SASS6 promoted the proliferation of esophageal cancer by inhibiting the p53 signaling pathway. SASS6 has potential as a novel tumor marker and a therapeutic target for ESCC.

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The positive feedback loop of RNASEH1-AS1/has-miR-218-5p/NET1 mediated by POU2F1 contributes to the development and progression of human lung squamous carcinoma

10.21203/rs.3.rs-18125/v1 ◽

2020 ◽

Author(s):

Jing-hao Jia ◽

Jing Wang ◽

Jia-rui Yu ◽

Peng Gao ◽

Yan-kun Liu ◽

...

Keyword(s):

Positive Feedback ◽

Feedback Loop ◽

Human Lung ◽

Squamous Carcinoma ◽

Carcinoma Cells ◽

Human Lung Cancer ◽

Migration And Invasion ◽

Positive Feedback Loop ◽

Squamous Carcinoma Cells ◽

Lung Squamous Carcinoma

Abstract Background In molecular level, competing endogenous RNAs (ceRNAs) regulates other RNA transcripts through competing for shared microRNAs (miRNA). miRNA negatively regulate gene expression at the levels of mRNAs stability and translation suppression. Methods We tested the mRNA level of miR-218-5p and RNASEH1-AS1 in clinical lung squamous cell carcinoma tissues by qRT-PCR. In the exploring of the role of miR-218-5p and RNASEH1-AS1 in the malignant phenotype of NCI-H520 cells, colony formation and MTT assay were used to test the cell viability and proliferation capability, trans-well invasion and wound healing assay were performed to examine the cell migration and invasion. ChIP assay was conducted to confirm the direct interact of POU2F1 and RNASEH1-AS1 promoter. Results In this investigation, we found that LncRNA RNASEH1-AS1 is up-regulated in human lung cancer, and serves as a miRNA sponge for hsa-miR-218-5p in human lung squamous carcinoma cells. lncRNA RNASEH1-AS1 facilitates growth and motility of lung squamous carcinoma cells, while miR-218-5p does the opposite. NET1 and POU2F1 are validated as direct and functional targets of miR-218-5p. The downregulation of miR-218-5p releases the suppression of NET1 and POU2F1. POU2F1 binds directly to the lncRNA-RNASEH1-AS1 promoter and acts as transcription factor to enhance the promoter activity of RNASEH1-AS1. Conclusion Above all, the positive feedback loop of RNASEH1-AS1/ hsa-miR-218-5p/ NET1/ POU2F1 can help us to understand the regulatory mechanism behind genesis and progression of human lung squamous carcinoma, possibly providing new biomarkers for its diagnosis and treatment.

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The positive RNASEH1-AS1/has-miR-218-5p/NET1 feedback loop mediated by POU2F1 contributes to the development and progression of human lung squamous carcinoma

10.21203/rs.3.rs-18125/v2 ◽

2020 ◽

Author(s):

Jing-hao Jia ◽

Jing Wang ◽

Jia-rui Yu ◽

Peng Gao ◽

Yan-kun Liu ◽

...

Keyword(s):

Feedback Loop ◽

Human Lung ◽

Lung Squamous Cell Carcinoma ◽

Squamous Carcinoma ◽

Carcinoma Cells ◽

Human Lung Cancer ◽

Migration And Invasion ◽

Squamous Carcinoma Cells ◽

Lung Squamous Carcinoma ◽

New Biomarkers

Abstract Background At the molecular level, competing endogenous RNAs (ceRNAs) regulate other RNA transcripts by competing for shared microRNAs (miRNA). Notably, miRNAs negatively regulate gene expression at the levels of mRNA stability and translation suppression.MethodsWe measured theexpression of miR-218-5p and RNASEH1-AS1 in clinical lung squamous cell carcinoma tissues using qRT-PCR. In an attempt to explore the roles of miR-218-5p and RNASEH1-AS1 in determining the malignant phenotype of NCI-H520 cells, colony formation and MTT assays were performed to measure cell viability and proliferation, and transwell invasion and wound healing assays were performed to examine cell migration and invasion. A ChIP assay was conducted to confirm the direct binding of POU2F1 to the RNASEH1-AS1 promoter.ResultsIn this investigation, the expression of the lncRNA RNASEH1-AS1 is upregulated in human lung cancer tissues, and it functions as a miRNA sponge for hsa-miR-218-5p in human lung squamous carcinoma cells. The lncRNA RNASEH1-AS1 facilitates the growth and motility of lung squamous carcinoma cells, while miR-218-5p exerts the opposite effects. NET1 and POU2F1 are validated as direct and functional targets of miR-218-5p. The downregulation of miR-218-5p releases the suppression of NET1 and POU2F1. POU2F1 binds directly to the lncRNA-RNASEH1-AS1 promoter and functions as transcription factor to enhance the promoter activity of RNASEH1-AS1.ConclusionsOverall, the positive RNASEH1-AS1/hsa-miR-218-5p/NET1/POU2F1 feedback loop can help us understand the regulatory mechanism underlying the genesis and progression of human lung squamouscarcinoma, possibly providing new biomarkers for its diagnosis and treatment.

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