Background: Circ-ZNF609 has been shown to modulate cancer progression in several kinds of cancer. However, the role of circ-ZNF609 played in lung adenocarcinoma (LAUD) remains unclear. In this study, we investigated the role of circ-ZNF609 in regulating LAUD cancer progression. Materials and Methods: Quantitative reverse transcription polymerase chain reaction was conducted to evaluate circ-ZNF609 expression in 52 LAUD tissues and 52 matched adjacent normal tissues, LAUD cell lines and bronchial epithelial cell line (HBE). The direct interaction between miR-1224-3p and circ-ZNF609 or EVT1 was verified using luciferase reporter assay and RNA immunoprecipitation assay. Cell Counting Kit-8, colony formation assay, cell-cycle analysis were utilized to examine the effect of circ-ZNF609 or miR-1224-3p on cell proliferation. Results: Circ-ZNF609 was significantly upregulated in LAUD tissues and cell lines, and its inhibition induced reduced cell proliferation of LAUD cells. Mechanistically, we demonstrated that circ-ZNF609 sponged miR-1224-3p to promote EVT1 expression. More importantly, miR-1224-3p overexpression strongly suppressed circZNF609-induced malignant phenotype of LAUD cells. Conclusion: Circ-ZNF609 enhances LAUD progression by increasing oncogenic EVT1 expression via sponging miR-1224-3p, revealing that circ-ZNF609/miR-1224-3p/ETV1 axis may be a promising therapeutic target for LAUD treatment.
Background: Numerous studies have shown that long noncoding RNAs play important roles in human cancer progression. Although zebrafish xenografts have recently become a novel in vivo model for human cancer research, whether such models can be used to study the function of long noncoding RNAs remains unknown. Methods: In vitro studies validated the roles of LINC00152 in the proliferation and invasion of lung cancer cells. In vivo studies of zebrafish xenografts also confirmed these roles of LINC00152. In vivo confocal imaging was used to more accurately evaluate the function of LINC00152 in cell proliferation and migration. Pharmacological experiments were further performed to study the potential ability of LINC00152 downregulation combined with an EGFR inhibitor to treat tumors in cultured cells and the zebrafish xenograft model. Results: Silencing of LINC00152 suppressed cell proliferation and invasion in SPCA1 and A549 lung cancer cell lines in vitro. In the zebrafish xenograft model, knockdown of LINC00152 reduced the proliferation and migration of lung cancer cells, as indicated by the two imaging methods at different magnifications. Moreover, the knockdown of LINC00152 enhanced the inhibition effect of afatinib for lung cancer progression in cultured cells and the zebrafish xenograft model. Conclusion: Our study reveals the oncogenic roles and potential for LINC00152 to be a target for tumor treatment in lung cancer using zebrafish xenograft models, and the findings suggest that this model could be used for functional and application studies of human long noncoding RNAs in tumor biology.
Background N6-methyladenosine (m6A) is the most common posttranscriptional modification of RNA and plays critical roles in human cancer progression. However, the biological function of m6A methylation requires further studied in cancer, especially in tumor angiogenesis. Methods A public database was used to analyze the expression and overall survival of ALKBH5 and PVT1 in lung cancer patients. CCK-8 and colony formation assays were performed to detect cell proliferation, a transwell assay was used to assess cell migration, and a tube formation assay was performed to assess angiogenic potential in vitro. A zebrafish lung cancer xenograft model was used to verify the function of ALKBH5 and PVT1 in vivo. Western blot assays were used to measure the relative protein expression in lung cancer cells. SRAMP predictor analysis and RNA stability experiments were used to examine the potential m6A modification. Results Bioinformatics analysis showed that the expression levels of m6A-related genes were changed significantly in lung cancer tissues compared with normal lung tissues. We then identified that ALKBH5 was upregulated in lung cancer tissues and associated with poor prognosis of lung cancer patients by analyzing a public database. Knockdown of ALKBH5 inhibited the proliferation and migration of cultured lung cancer cell lines. Zebrafish lung cancer xenografts showed that ALKBH5 silencing also suppressed the growth and metastasis of lung cancer cells. Moreover, knockdown of ALKBH5 inhibited the angiogenesis of lung cancer in vitro and in vivo. Mechanistic studies showed that knockdown of ALKBH5 decreased the expression and stability of PVT1 in lung cancer cells. We next observed that PVT1 promoted the progression of lung cancer cells in vitro and in vivo and regulated the expression of VEGFA and angiogenesis in lung cancer. Finally, rescue experiments revealed that ALKBH5 regulated the proliferation, migration and angiogenesis of lung cancer cells, partially through PVT1. Conclusion Our results demonstrate that ALKBH5 promotes the progression and angiogenesis of lung cancer by regulating the expression and stability of PVT1, which provides a potential prognostic and therapeutic target for lung cancer patients.
The present research was to investigate the effects of skimmianine (SK) in four non-small cell lung cancer (NSCLC) cells. We found that SK can significantly inhibit the growth of NSCLC cells and markedly induce apoptosis in NSCLC cells. The effects of growth inhibition and apoptosis induction were in a concentration-response relationship and caspase-dependent manner.
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