HOXD13 promotes the malignant progression of colon cancer by upregulating PTPRN2

Ding

Oxidative Medicine and Cellular Longevity

et al. 2022

Wumei Pill (WMP) is a traditional Chinese herbal formulation and widely used to treat digestive system diseases in clinical. S-Adenosylhomocysteine hydrolase (AHCY) can catalyze the hydrolysis of S-adenosylhomocysteine to adenosine and homocysteine in living organisms, and its abnormal expression is linked to the pathogenesis of many diseases including colorectal cancer (CRC). A previous study reported that WMP could prevent CRC in mice; however, the underlying mechanisms especially the roles of AHCY in WMP-induced anti-CRC remain largely unknown. Here, we investigated the regulatory roles and potential mechanisms of AHCY in WMP-induced anti-CRC. WMP notably alleviated the azoxymethane/dextran sulfate sodium- (AOM/DSS-) induced colitis-associated colon cancer (CAC) in mice. Besides, WMP inhibited the inflammation and oxidative stress in AOM/DSS-induced CAC mice. AHCY was high expression in clinical samples of colon cancer compared to the adjacent tissues. WMP inhibited the AHCY expression in AOM/DSS-induced CAC mice. An in vitro study found that AHCY overexpression induced cell proliferation, colony formation, invasion, and tumor angiogenesis, whereas its knockdown impaired its oncogenic function. AHCY overexpression enhanced, while its knockdown weakened the inflammation and oxidative stress in colon cancer cells. Interestingly, WMP potently suppressed the hedgehog (Hh) signaling in AOM/DSS-induced CAC mice. A further study showed that AHCY overexpression activated the Hh signaling while AHCY knockdown inactivated the Hh signaling. Moreover, activation of the Hh signaling reversed the effect of AHCY silencing on inflammation and oxidative stress in vitro. In conclusion, WMP alleviated the AOM/DSS-induced CAC through inhibition of inflammation and oxidative stress by regulating AHCY-mediated hedgehog signaling in mice. These findings uncovered a potential molecular mechanism underlying the anti-CAC effect of WMP and suggested WMP as a promising therapeutic candidate for CRC.

“…Transwell Invasion Assay. Transwell experiment was used to detect cell invasion ability as reported previously [52]. Briefly, matrixgel was spread onto the upper chamber.…”

Section: Cck8 Assaymentioning

confidence: 99%

Wumei Pill Ameliorates AOM/DSS-Induced Colitis-Associated Colon Cancer through Inhibition of Inflammation and Oxidative Stress by Regulating S-Adenosylhomocysteine Hydrolase- (AHCY-) Mediated Hedgehog Signaling in Mice

Ding

Oxidative Medicine and Cellular Longevity

et al. 2022

“…Among the top 100 DNA methylation sites in the BLCA network, multiple sites, such as cg24701780, cg24804145, cg15192120, and cg25497530, are all located on the PTPRN2 gene, and the average correlation between them was

, which was larger than that averaged over the top 100 DNA methylation sites. This gene encodes a protein with sequence similarity to the receptor-like protein tyrosine phosphatase, which accelerates cancer progression and metastasis [ 72 , 73 ]. In Table S3 , we summarize the correlation coefficients for the sites on the same gene.…”

Section: Resultsmentioning

confidence: 99%

Identifying Tumor-Associated Genes from Bilayer Networks of DNA Methylation Sites and RNAs

Gao

Zhu

et al. 2022

Life

Network theory has attracted much attention from the biological community because of its high efficacy in identifying tumor-associated genes. However, most researchers have focused on single networks of single omics, which have less predictive power. With the available multiomics data, multilayer networks can now be used in molecular research. In this study, we achieved this with the construction of a bilayer network of DNA methylation sites and RNAs. We applied the network model to five types of tumor data to identify key genes associated with tumors. Compared with the single network, the proposed bilayer network resulted in more tumor-associated DNA methylation sites and genes, which we verified with prognostic and KEGG enrichment analyses.

“…The 2q31.1 region is resided mainly by HOXD genes. Previous studies in other cancer types have suggested a potential oncogenic role for HOXD genes, but the underlying mechanism is not clear [21,22,40]. Inhibition of the transcription of the HOXD locus was suggested to be relevant with tumor-cell immune escape [41].…”

Section: Discussionmentioning

confidence: 99%

Dysregulated Immune and Metabolic Microenvironment Is Associated with the Post-Operative Relapse in Stage I Non-Small Cell Lung Cancer

Zhang

Xiao²,

Zhu³

et al. 2022

Cancers

The underlying mechanism of post-operative relapse of non-small cell lung cancer (NSCLC) remains poorly understood. We enrolled 57 stage I NSCLC patients with or without relapse and performed whole-exome sequencing (WES) and RNA sequencing (RNA-seq) on available primary and recurrent tumors, as well as on matched tumor-adjacent tissues (TATs). The WES analysis revealed that primary tumors from patients with relapse were enriched with USH2A mutation and 2q31.1 amplification. RNA-seq data showed that the relapse risk was associated with aberrant immune response and metabolism in the microenvironment of primary lesions. TATs from the patients with relapse showed an immunosuppression state. Moreover, recurrent lesions exhibited downregulated immune response compared with their paired primary tumors. Genomic and transcriptomic features were further subjected to build a prediction model classifying patients into groups with different relapse risks. We show that the recurrence risk of stage I NSCLC could be ascribed to the altered immune and metabolic microenvironment. TATs might be affected by cancer cells and facilitate the invasion of tumors. The immune microenvironment in the recurrent lesions is suppressed. Patients with a high risk of relapse need active post-operative intervention.