Identification of HAGHL as a novel metabolic oncogene regulating human colorectal cancer progression

Xu, Yan; Zhou, Xiaojun; Gao, Ling; Su, Yan; Li, Zhenyun; Zhang, Daiyi; Pu, Jianhong; Zou, Shitao; Mao, Zhongqi

doi:10.1007/s12094-022-03008-1

Cited by 2 publications

(2 citation statements)

References 29 publications

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“…38 HAGHL is a newly discovered metabolic oncogene and has been associated with the progression of human colorectal cancer. 39 CCDC85B and TNFRSF4 were discovered and validated as genes associated with placebo effects. The expression of CCDC85B is regulated in a p53-dependent manner (p-53 has anti-oncogenic actions blocking βcatenin-dependent gene expression in the nucleus).…”

Section: Discussionmentioning

confidence: 99%

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Transcriptomic Profiles Associated with Experimental Placebo Effects in Chronic Pain

Colloca,

Mocci,

Wang

et al. 2024

Clin Pharma and Therapeutics

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Gene expression networks associated with placebo effects are understudied; in this study, we identified transcriptomic profiles associated with placebo responsivity. Participants suffering from chronic pain underwent a verbal suggestion and conditioning paradigm with individually tailored thermal painful stimulations to elicit conditioned placebo effects. Participants reported pain intensity on a visual analog scale (VAS) anchored from zero = no pain to 100 = maximum imaginable pain. RNA was extracted from venous blood and RNA sequencing and validation tests were performed to identify differentially expressed genes (DEGs) associated with placebo effects, controlling for sex and level of pain. Unbiased enrichment analyses were performed to identify biological processes associated with placebo effects. Of the 10,700 protein‐coding genes that passed quality control filters, 667 were found to be associated with placebo effects (FDR <0.05). Most genes (97%) upregulated were associated with larger placebo effects. The 17 top transcriptome‐wide significant genes were further validated via RT‐qPCR in an independent cohort of chronic pain participants. Six of them (CCDC85B, FBXL15, HAGH, PI3, SELENOM, and TNFRSF4) showed positive and significant (P < 0.05) correlation with placebo effects in the cohort. The overall DEGs were highly enriched in regulation of expression of SLITs and ROBOs (R‐HSA‐9010553, FDR = 1.26e−33), metabolism of RNA (R‐HSA‐8953854, FDR = 1.34e−30), Huntington's disease (hsa05016, FDR = 9.84e−31), and ribosome biogenesis (GO:0042254, FDR = 2.67e−15); alternations in these pathways might jeopardize the proneness to elicit placebo effects. Future studies are needed to replicate this finding and better understand the unique molecular dynamics of people who are more or less affected by pain and placebo.

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Section: Discussionmentioning

confidence: 99%

“…FBXL15 plays a role in the G2/M transition of the cell cycle, as well as in cellular protein metabolic processes and the positive regulation of the bone morphogenetic proteins signaling pathway 38 . HAGHL is a newly discovered metabolic oncogene and has been associated with the progression of human colorectal cancer 39 …”

Section: Discussionmentioning

confidence: 99%

Transcriptomic Profiles Associated with Experimental Placebo Effects in Chronic Pain

Colloca,

Mocci,

Wang

et al. 2024

Clin Pharma and Therapeutics

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Intron retention as an excellent marker for diagnosing depression and for discovering new potential pathways for drug intervention

Okada,

Oshima,

Maruko

et al. 2024

Front. Psychiatry

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BackgroundPeripheral inflammation is often associated with depressive disorders, and immunological biomarkers of depression remain a focus of investigation.MethodsWe performed RNA-seq analysis of RNA transcripts of human peripheral blood mononuclear cells from a case-control study including subjects with self-reported depression in the pre-symptomatic state of major depressive disorder and analyzed differentially expressed genes (DEGs) and the frequency of intron retention (IR) using rMATS.ResultsAmong the statistically significant DEGs identified, the 651 upregulated DEGs were particularly enriched in the term “bacterial infection and phagocytosis”, whereas the 820 downregulated DEGs were enriched in the terms “antigen presentation” and “T-cell proliferation and maturation”. We also analyzed 158 genes for which the IR was increased (IncIR) and 211 genes for which the IR was decreased (DecIR) in the depressed subjects. Although the Gene Ontology terms associated with IncIR and DecIR were very similar to those of the up- and downregulated genes, respectively, IR genes appeared to be particularly enriched in genes with sensor functions, with a preponderance of the term “ciliary assembly and function”. The observation that IR genes specifically interact with innate immunity genes suggests that immune-related genes, as well as cilia-related genes, may be excellent markers of depression. Re-analysis of previously published RNA-seq data from patients with MDD showed that common IR genes, particularly our predicted immune- and cilia-related genes, are commonly detected in populations with different levels of depression, providing validity for using IR to detect depression.ConclusionDepression was found to be associated with activation of the innate immune response and relative inactivation of T-cell signaling. The DEGs we identified reflect physiological demands that are controlled at the transcriptional level, whereas the IR results reflect a more direct mechanism for monitoring protein homeostasis. Accordingly, an alteration in IR, namely IncIR or DecIR, is a stress response, and intron-retained transcripts are sensors of the physiological state of the cytoplasm. The results demonstrate the potential of relative IR as a biomarker for the immunological stratification of depressed patients and the utility of IR for the discovery of novel pathways involved in recovery from depression.

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Identification of HAGHL as a novel metabolic oncogene regulating human colorectal cancer progression

Cited by 2 publications

References 29 publications

Transcriptomic Profiles Associated with Experimental Placebo Effects in Chronic Pain

Transcriptomic Profiles Associated with Experimental Placebo Effects in Chronic Pain

Intron retention as an excellent marker for diagnosing depression and for discovering new potential pathways for drug intervention

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