Project description:The homeobox (HOX) family encodes highly conserved transcription factors and plays a crucial role in embryonic development and tumorigenesis. Homeobox D1 (HOXD1) is a member of the HOX family, whose biological functions in lung cancer are unclear. The UALCAN database analysis of HOXD1 expression patterns revealed that HOXD1 is downregulated in lung adenocarcinoma patient samples relative to adjacent normal tissue. Western blotting validated low HOXD1 expression in lung adenocarcinoma (LUAD) cell lines. The Kaplan-Meier plotter database demonstrated that HOXD1 expression reduction in LUAD was found to correlate with worse overall survival. Meanwhile, in vitro study showed that HOXD1 overexpression suppressed LUAD cells proliferation, migration, and invasion. In the mouse tumor model, upregulated HOXD1 retarded tumor growth. In addition, targeted bisulfite sequencing and ChIP assay found that DNA hypermethylation occurred in the promoter region of the HOXD1 gene and was associated with DNA methyltransferases. In additionMoreover, upregulated HOXD1 as a transcriptional factor increased the transcriptional expression of BMP2 and BMP6. Taken together, the dysregulation of HOXD1 mediated by DNA methylation inhibited the initiation and progression of lung adenocarcinoma by regulating the expression of BMP/BMP6.
Project description:The homeobox (HOX) family encodes highly conserved transcription factors and plays a crucial role in embryonic development and tumorigenesis. Homeobox D1 (HOXD1) is a member of the HOX family, whose biological functions in lung cancer are unclear. The UALCAN database analysis of HOXD1 expression patterns revealed that HOXD1 is downregulated in lung adenocarcinoma patient samples relative to adjacent normal tissue. Western blotting validated low HOXD1 expression in lung adenocarcinoma (LUAD) cell lines. The Kaplan-Meier plotter database demonstrated that HOXD1 expression reduction in LUAD was found to correlate with worse overall survival. Meanwhile, in vitro study showed that HOXD1 overexpression suppressed LUAD cells proliferation, migration, and invasion. In the mouse tumor model, upregulated HOXD1 retarded tumor growth. In addition, targeted bisulfite sequencing and ChIP assay found that DNA hypermethylation occurred in the promoter region of the HOXD1 gene and was associated with DNA methyltransferases. In additionMoreover, upregulated HOXD1 as a transcriptional factor increased the transcriptional expression of BMP2 and BMP6. Taken together, the dysregulation of HOXD1 mediated by DNA methylation inhibited the initiation and progression of lung adenocarcinoma by regulating the expression of BMP/BMP6.
Project description:Purpose: Lung adenocarcinoma tumors acquire resistance to the newly-developed as well as existing therapies that restricts life quality improvements. The goal of the current study is to investigate the noncoding portion of the human transcriptome in search of actionable targets for lung adenocarcinoma treatment. Methods: The identified actionable targets (LY6K-AS lncRNA and YWHAG) were transiently downregulated in A549 cell line using either LNA-GapmeRs or siRNA. RNA was extracted from each sample and analyzed in respect to the corresponding control. Results: LY6K-AS lncRNA regulated mitotic progression in A549 cell line through the interaction with YWHAG to orchestrate the expression of several mitosis-promoting factors. Conclusions: Our study indicates that LY6K-AS silencing is a promising therapeutic option for LUAD that inhibits oncogenic mitotic progression.