Acetylation of PHF5A Modulates Stress Responses and Colorectal Carcinogenesis through Alternative Splicing-Mediated Upregulation of KDM3A

Wang, Zhe; Yang, Xin; Liu, Cheng; Li, Xin; Zhang, Buyu; Wang, Bo; Zhang, Yu; Song, Chen; Zhang, Tianzhuo; Liu, Minghui; Liu, Boya; Ren, Mengmeng; Jiang, Hongpeng; Zhang, Junhua; Liu, Xiaoyun; Zhang, Hongquan; Zhu, Weiguo; Yin, Yuxin; Zhang, Zhang; Gu, Wei; Luo, Jianyuan

doi:10.1016/j.molcel.2019.04.009

Cited by 69 publications

(65 citation statements)

References 41 publications

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“…Many studies have reported that histone demethylases were upregulated in human cancers (11,(33)(34)(35). However, it is still unclear whether this is a bystander event or a driver of tumorigenesis.…”

Section: Discussionmentioning

confidence: 99%

Histone Demethylase JMJD1A Promotes Tumor Progression via Activating Snail in Prostate Cancer

Tang

Dai

Fan

et al. 2020

Molecular Cancer Research

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The histone demethylase JMJD1A plays a key functional role in spermatogenesis, sex determination, stem cell renewal, and cancer via removing mono-and di-methyl groups from H3K9 to epigenetically control gene expression. However, its role in prostate cancer progression remains unclear. Here, we found JMJD1A was significantly elevated in prostate cancer tissue compared with matched normal tissue. Ectopic JMJD1A expression in prostate cancer cells promoted proliferation, migration, and invasion in vitro, and tumorigenesis in vivo; JMJD1A knockdown exhibited the opposite effects. Mechanically, we revealed that JMJD1A directly interacted with the Snail gene promoter and regulated its transcriptional activity, promoting prostate cancer progression both in vitro and in vivo. Furthermore , we found that JMJD1A transcriptionally activated Snail expression via H3K9me1 and H3K9me2 demethylation at its special promoter region. In summary, our studies reveal JMJD1A plays an important role in regulating proliferation and progression of prostate cancer cells though Snail, and thus highlight JMJD1A as potential therapeutic target for advanced prostate cancer. Implications: Our studies identify that JMJD1A promotes the proliferation and progression of prostate cancer cells through enabling Snail transcriptional activation, and thus highlight JMJD1A as potential therapeutic target for advanced prostate cancer.

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Section: Discussionmentioning

confidence: 99%

Histone Demethylase JMJD1A Promotes Tumor Progression via Activating Snail in Prostate Cancer

Tang

Dai

Fan

et al. 2020

Molecular Cancer Research

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“…Seven genes (ACO2, FOXD1, LMAN2, PHF5A, PRR7, PRR7-AS1, and SKAP2) were implicated in both HNs and colonoids; FOXD1, PRR7, and SKAP2 encode proteins with known roles in immune regulation, [50][51][52] and PHF5A mediates stress resistance in a model of colorectal cancer. 53…”

Section: Q22mentioning

confidence: 99%

Variant-to-Gene-Mapping Analyses Reveal a Role for the Hypothalamus in Genetic Susceptibility to Inflammatory Bowel Disease

Lasconi¹,

Pahl²,

Cousminer³

et al. 2021

Cellular and Molecular Gastroenterology and Hepatology

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IBD genetic risk profile Non IBD genetic risk profile Dysfunctional stress responses STRESS Flares Functional stress responses SUMMARY Inflammatory bowel disease is associated with stress and depression. These 2 comorbidities are influenced by the hypothalamus. Integrating our 3-dimensional genomic data with publicly available genome-wide association study data, our results implicate a subset of inflammatory bowel disease loci conferring their effect via the hypothalamus. Our findings warrant further investigation.

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“…Recently, one study reported that SF3b7 is acetylated mainly at its Lys29 residue under nutrient starvation [79]. The study further found that this modification enhances the interaction between SF3b7 and other SF3b components and changes the cellular pre-mRNA splicing patterns.…”

Section: Modifications Of Sf3bmentioning

confidence: 83%

“…The SF3b complex appears like a flaming torch with SF3b1 on the upper flame part, SF3b3 on the lower torch part and other subunits dotted within or around. The modification-related residues of SF3b1 (Thr434), SF3b2 (Arg508), and SF3b7 (Lys29) are indicated with red circles and colored in black [73,78,79]. The right panel shows three views of the SF3b complex in surface mode.…”

Section: Introductionmentioning

confidence: 99%

The SF3b complex: splicing and beyond

Sun¹

2020

Cell. Mol. Life Sci.

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The SF3b complex is an intrinsic component of the functional U2 small nuclear ribonucleoprotein (snRNP). As U2 snRNP enters nuclear pre-mRNA splicing, SF3b plays key roles in recognizing the branch point sequence (BPS) and facilitating spliceosome assembly and activation. Since the discovery of SF3b, substantial progress has been made in elucidating its molecular mechanism during splicing. In addition, numerous recent studies indicate that SF3b and its components are engaged in various molecular and cellular events that are beyond the canonical role in splicing. This review summarizes the current knowledge on the SF3b complex and highlights its multiple roles in splicing and beyond.

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Acetylation of PHF5A Modulates Stress Responses and Colorectal Carcinogenesis through Alternative Splicing-Mediated Upregulation of KDM3A

Cited by 69 publications

References 41 publications

Histone Demethylase JMJD1A Promotes Tumor Progression via Activating Snail in Prostate Cancer

Histone Demethylase JMJD1A Promotes Tumor Progression via Activating Snail in Prostate Cancer

Variant-to-Gene-Mapping Analyses Reveal a Role for the Hypothalamus in Genetic Susceptibility to Inflammatory Bowel Disease

The SF3b complex: splicing and beyond

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