ANKRD29, as a new prognostic and immunological biomarker of non-small cell lung cancer, inhibits cell growth and migration by regulating MAPK signaling pathway.

Background: The predominant cancer-related deaths worldwide are caused by lung cancer, particularly non-small cell lung cancer (NSCLC), despite the fact that numerous therapeutic initiatives have been devised to improve the outcomes. Ankyrin repeat domain (ANKRD) is one of the widespread protein structural motifs in eukaryotes but the functions of ANKRD proteins in NSCLC progression remains unclear.

Methods: We performed integrative bioinformatical analysis to determine the dysregulated expression of ANKRDs in multiple tumors and the association between ANKRD29 expression and the NSCLC tumor environment.

IKZF4 acts as a novel tumor suppressor in non-small cell lung cancer by suppressing Notch signaling pathway.

Non-small cell lung cancer (NSCLC) is the predominant cause of cancer-related mortality globally, although many clinical efforts have been developed to improve the outcomes. The Ikaros zing-finger family transcription factors (IKZFs) have been proved to play pivotal roles in lymphopoiesis and myeloma progression, but their roles in solid tumors development remain unclear. We performed integrative bioinformatical analysis to determine the dysregulation expression of IKZFs in multiple tumors and the correlation between IKZF4 and NSCLC tumor environment.

Synthesis and biological evaluation of cholic acid-conjugated oxaliplatin as a new prodrug for liver cancer.

A cholic acid-conjugated oxaliplatin, LLC-202, is developed as a novel prodrug for liver cancer. The conjugate is obtained by using 3-NHcyclobutane-1,1-dicarboxylate as a linker between the oxaliplatin analogue and cholic acid moiety and cholic acid is strongly bonded to the linker via an amide bond. Pharmacokinetic experiment shows that LLC-202 is mainly distributed and accumulated in the liver after intravenous administration to Sprague-Dawley rats, revealing the liver-targeting profile.

MrgprF acts as a tumor suppressor in cutaneous melanoma by restraining PI3K/Akt signaling.

The incidence of cutaneous melanoma (CM) has been increasing annually worldwide. In this study, we identify that MrgprF, a MAS related GPR family member, is decreased in cutaneous melanoma tissues and cell lines due to hypermethylation of its promoter region, and show that patients with CM expressing high levels of MrgprF exhibit an improved clinical outcome. We demonstrate that MrgprF forced expression inhibits tumor cell proliferation, migration, xenograft tumor growth, and metastasis.

Hypoxia-induced GLT8D1 promotes glioma stem cell maintenance by inhibiting CD133 degradation through N-linked glycosylation.

Gliomas are the most aggressive primary brain tumors. However, no significant improvement in survival has been achieved with the addition of temozolomide (TMZ) or radiation as initial therapy, although many clinical efforts have been carried out to target various signaling pathways or putative driver mutations. Here, we report that glycosyltransferase 8 domain containing 1 (GLT8D1), induced by HIF-1α under a hypoxic niche, significantly correlates with a higher grade of glioma, and a worse clinical outcome.

LncRNA PKMYT1AR promotes cancer stem cell maintenance in non-small cell lung cancer via activating Wnt signaling pathway.

Background: Non-small cell lung cancer (NSCLC) is the most common type of human lung cancers, which has diverse pathological features. Although many signaling pathways and therapeutic targets have been defined to play important roles in NSCLC, limiting efficacies have been achieved.

Methods: Bioinformatics methods were used to identify differential long non-coding RNA expression in NSCLC.

Mutation Selected for Hypoxia Adaptation Inhibits Tumor Growth.

Hypoxia occurs not only in natural environments including high altitude, underground burrows and deep sea, but also in human pathological conditions, such as hypoxic solid tumors. It has been well documented that hypoxia related signaling pathway is associated with a poor clinical outcome. Our group has recently identified multiple novel genes critical for solid tumor growth comparing the genome-wide convergent/parallel sequence evolution of highland mammals.

3D Genome of macaque fetal brain reveals evolutionary innovations during primate corticogenesis.

Elucidating the regulatory mechanisms of human brain evolution is essential to understanding human cognition and mental disorders. We generated multi-omics profiles and constructed a high-resolution map of 3D genome architecture of rhesus macaque during corticogenesis. By comparing the 3D genomes of human, macaque, and mouse brains, we identified many human-specific chromatin structure changes, including 499 topologically associating domains (TADs) and 1,266 chromatin loops.

Convergent genomic signatures of high-altitude adaptation among domestic mammals.

Abundant and diverse domestic mammals living on the Tibetan Plateau provide useful materials for investigating adaptive evolution and genetic convergence. Here, we used 327 genomes from horses, sheep, goats, cattle, pigs and dogs living at both high and low altitudes, including 73 genomes generated for this study, to disentangle the genetic mechanisms underlying local adaptation of domestic mammals. Although molecular convergence is comparatively rare at the DNA sequence level, we found convergent signature of positive selection at the gene level, particularly the gene in these Tibetan domestic mammals.

PAQR4 promotes chemoresistance in non-small cell lung cancer through inhibiting Nrf2 protein degradation.

Lung cancer is the leading cause of cancer related deaths worldwide. We have previously identified many differentially expressed genes (DEGs) from large scale pan-cancer dataset using the Cross-Value Association Analysis (CVAA) method. Here we focus on Progestin and AdipoQ Receptor 4 (PAQR4), a member of the progestin and adipoQ receptor (PAQR) family localized in the Golgi apparatus, to determine their clinical role and mechanism in the development of non-small cell lung cancer (NSCLC).

YTHDF1 links hypoxia adaptation and non-small cell lung cancer progression.

Hypoxia occurs naturally at high-altitudes and pathologically in hypoxic solid tumors. Here, we report that genes involved in various human cancers evolved rapidly in Tibetans and six Tibetan domestic mammals compared to reciprocal lowlanders. Furthermore, mA modified mRNA binding protein YTHDF1, one of evolutionary positively selected genes for high-altitude adaptation is amplified in various cancers, including non-small cell lung cancer (NSCLC).

Author Correction: Comprehensive integrative analyses identify GLT8D1 and CSNK2B as schizophrenia risk genes.

In the original version of this Article, the affiliation details for Qiushuo Shen incorrectly omitted 'Kunming College of Life Science, University of Chinese Academy of Sciences, Kunming, 650204, China'. This has now been corrected in both the PDF and HTML versions of the Article.

Comprehensive integrative analyses identify GLT8D1 and CSNK2B as schizophrenia risk genes.

Recent genome-wide association studies (GWAS) have identified multiple risk loci that show strong associations with schizophrenia. However, pinpointing the potential causal genes at the reported loci remains a major challenge. Here we identify candidate causal genes for schizophrenia using an integrative genomic approach.

GRK5 functions as an oncogenic factor in non-small-cell lung cancer.

Lung cancer is the leading cause of cancer-related deaths worldwide, and non-small-cell lung cancer (NSCLC) accounts for about 80% of all cases, which is the major subgroup of lung cancer. G protein-coupled receptor kinase 5 (GRK5) has been demonstrated to play pivotal roles in both development and progression of several pathological conditions including cancer. Here, we found that GRK5 expression was significantly increased in 539 NSCLC cancerous tissues than that in 99 normal non-cancerous tissues by immunohistochemistry analysis; we also showed intensive higher positive staining percentage in female and adenocarcinoma (ADC) NSCLC patients than that in male and squamous cell carcinoma (SCC) patients, respectively.

Establishment of basal cell carcinoma animal model in Chinese tree shrew ().

Basal cell carcinoma (BCC) is the most common skin cancer worldwide, with incidence rates continuing to increase. Ultraviolet radiation is the major environmental risk factor and dysregulation of the Hedgehog (Hh) signaling pathway has been identified in most BCCs. The treatment of locally advanced and metastatic BBCs is still a challenge and requires a better animal model than the widely used rodents for drug development and testing.

A Normalization-Free and Nonparametric Method Sharpens Large-Scale Transcriptome Analysis and Reveals Common Gene Alteration Patterns in Cancers.

Heterogeneity in transcriptional data hampers the identification of differentially expressed genes (DEGs) and understanding of cancer, essentially because current methods rely on cross-sample normalization and/or distribution assumption-both sensitive to heterogeneous values. Here, we developed a new method, Cross-Value Association Analysis (CVAA), which overcomes the limitation and is more robust to heterogeneous data than the other methods. Applying CVAA to a more complex pan-cancer dataset containing 5,540 transcriptomes discovered numerous new DEGs and many previously rarely explored pathways/processes; some of them were validated, both and , to be crucial in tumorigenesis, e.

NCAPH plays important roles in human colon cancer.

Colon cancer (CC) is one of the major malignancies worldwide, whose pathogenesis is complex and requires the accumulated alteration of multiple genes and signaling pathways. Condensins are multi-protein complexes that play pivotal roles in chromosome assembly and segregation during mitosis, meiosis and even tumorigenesis. Using tissue microarrays by immunohistochemistry and hematoxylin-eosin staining, we found that non-SMC condensin I complex subunit H (NCAPH) in colon cancerous tissues was higher than that in all corresponding adjacent non-cancerous tissues.

Indole alkaloids with new skeleton activating neural stem cells.

Alstoscholarisines A-E (1-5), five unprecedented monoterpenoid indole alkaloids with 6/5/6/6/6 fused-bridge rings, were isolated from Alstonia scholaris. They promoted adult neuronal stem cells (NSCs) proliferation significantly, in which the most active one (1) functioned from a concentration of 0.1 μg/mL in a dosage-dependent manner.