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Glioblastoma multiforme (GBM) is a highly malignant brain tumor where new biomarkers and drug targets are much needed in the oncology clinic. miR-433 was identified as a tumor-suppressing miRNA in several different types of human cancer. However, the integrative biology of miR-433 in GBM is still largely unknown. By analyzing the expression profiles of miR-433 in 198 patients with glioma at The Cancer Genome Atlas, we found that the miR-433 expression was decreased in glioma whereas the low expression of miR-433 was significantly associated with shorter overall survival. We then conducted in vitro studies and demonstrated that increased expression of miR-433 suppressed the proliferation, migration, and invasion of LN229 and T98G cells, two representative glioma cell lines. Further, using in vivo mouse model, we found that upregulation of miR-433 inhibited the tumor growth of glioma cells. To situate the integrative biology understanding of the action of miR-433 in glioma, we identified ERBB4 as a gene targeted directly by miR-433 in LN229 and T98G cells. Overexpressed ERBB4 rescued the phenotype caused by overexpression of miR-433. Finally, we showed that miR-433 suppressed the PI3K/Akt pathway in glioma cells. In conclusion, our study demonstrated that miR-433 could potentially act as a tumor suppressor for GBM and may serve as a potential therapeutic target for GBM. Further integrative biology and clinical translational research are warranted to evaluate miR-433 in GBM.

Objective: Ankyrin repeat domain-containing protein 6 (ANKRD6) is an ankyrin repeat-containing protein which is structurally related to vertebrate inversin and Drosophila Diego. However, the correlations between ANKRD6 and tumor-infiltrating immune cells in cancers is not clear., Methods: ANKRD6 expression was analyzed by Oncomine, Tumor Immune Estimation Resource (TIMER) and Gene Expression Profiling Interactive Analysis (GEPIA). PrognoScan and GEPIA were used to evaluate the influence of ANKRD6 on clinical prognosis. TIMER and CIBERSORT were used to analyze correlations between ANKRD6 expression levels and tumor immune cell infiltrates. Immunohistochemical analysis of the relationship between ANKRD6 expression and overall survival, as well as the relationship between ANKRD6 expression and M2 macrophage infiltration, was performed., Results: High level of ANKRD6 expression was associated with poor prognosis of colon cancer. ANKRD6 expression level was positively correlated with infiltrating levels of CD8+ T cells, CD4+ T cells, macrophages, neutrophils and dendritic cells in colon cancer by using TIMER. Using CIBERSORT, we found that in plasma cells, CD8+ T cells, CD4+ memory resting T cells, follicular helper T cells and activated natural killer cells were significantly lower in the ANKRD6-high group than in the ANKRD6-low group. M0 and M2 macrophages were significantly higher in the ANKRD6-high group than in the ANKRD6-low group. Immunohistochemistry confirmed that M2 macrophage infiltration in the ANKRD6-high group significantly increased., Conclusions: The high ANKRD6 expression is associated with poor prognosis of colon cancer. ANKRD6 expression is positively correlated with M2 macrophage infiltration in colon cancer., (Copyright © 2021 Chinese Journal of Cancer Research. All rights reserved.)

It is widely accepted that some messenger RNAs are evolutionarily conserved across species, both in sequence and tissue-expression specificity. To date, however, little effort has been made to exploit the transcriptome divergence between cancer and adjacent normal tissue at the pan-organ level. In this work, a transcriptome sequencing dataset from 675 normal-tumor pairs, representing 21 solid organs in The Cancer Genome Atlas, is used to evaluate expression evolution. The results show that in most cancer types, gene expression divergence and organ-specificity are reduced in cancer tissue compared to adjacent normal tissue. Furthermore, we observe that all cancers share cell cycle dysregulation through interrogating differentially expressed protein coding genes. Meanwhile, weighted correlation network analysis is used to detect of the gene module structure variation between cancer and adjacent normal tissue. And modules consisting of tightly co-regulated genes in cancer change substantially compared with those in adjacent normal tissue. We thus assume that the destruction of a coordinated regulatory network might result in tumorigenesis and tumor progression. Our results provide new insights into the complex cancer biology and shed light on the mysterious regulation mode for cancer.