MicroRNA-30c-2-3p represses malignant progression of gastric adenocarcinoma cells via targeting ARHGAP11A

Zheng, Liang; Cai, Xiongchao; Song, Jintian; Shi, Huaijing; Zhang, Jiulong; Ke, Xi; Li, Hui; Chen, Yigui

doi:10.1080/21655979.2022.2090222

Cited by 4 publications

(2 citation statements)

References 35 publications

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“…3 h), and this underscores the strict sex-dependent regulation of miRNA in tobacco smoke exposed animals. Specifically, we identified 3 repressed DEMs in tobacco smoke exposed WT females of which miR-30c-2-3p and miR-339-5p function as tumor suppressors by targeting Rho GTPase activating protein 11A (Zheng et al 2022 ), and BCL6 (Li et al 2018 ), and repression of miR-151-5p inhibits cell proliferation in LC (Daugaard et al 2017 ). In the same comparison we identified 7 DEMs specifically repressed in WT males and this included two to fourfold repressed miR-1224-5p, miR-574-3p and miR-466f-3p.…”

Section: Resultsmentioning

confidence: 99%

Sex differences in the tumor promoting effects of tobacco smoke in a cRaf transgenic lung cancer disease model

Zhong,

Borlak

2024

Arch Toxicol

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Tobacco smoke (TS) is the leading cause for lung cancer (LC), and female smokers are at a greater risk for LC. Yet, the underlying causes are unknown. We performed whole genome scans in TS exposed wild type and histologically characterized tumor lesions of cRaf transgenic mice. We constructed miRNA-gene and transcription factor-miRNA/gene regulatory networks and determined sex-specific gene regulations by evaluating hormone receptor activities. We validated the findings from TS exposed cRaf mice in a large cohort of smoking and never-smoking LC patients. When compared to males, TS prompted a sevenfold increase in tumor multiplicity in cRaf females. Genome-wide scans of tumor lesions identified 161 and 53 genes and miRNAs, which code for EGFR/MAPK signaling, cell proliferation, oncomirs and oncogenes, and 50% of DEGs code for immune response and tumor evasion. Outstandingly, in transgenic males, TS elicited upregulation of 20 tumor suppressors, some of which are the targets of the androgen and estrogen receptor. Conversely, in females, 18 tumor suppressors were downregulated, and five were specifically repressed by the estrogen receptor. We found TS to perturb the circadian clock in a sex-specific manner and identified a female-specific regulatory loop that consisted of the estrogen receptor, miR-22-3p and circadian genes to support LC growth. Finally, we confirmed sex-dependent tumor promoting effects of TS in a large cohort of LC patients. Our study highlights the sex-dependent genomic responses to TS and the interplay of circadian clock genes and hormone receptors in the regulation of oncogenes and oncomirs in LC growth.

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Section: Resultsmentioning

confidence: 99%

Sex differences in the tumor promoting effects of tobacco smoke in a cRaf transgenic lung cancer disease model

Zhong,

Borlak

2024

Arch Toxicol

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“…3g), and this underscores the strict sex-dependence to cRaf and tobacco smoke. Speci cally, we identi ed 3 repressed DEMs in tobacco smoke exposed WT females of which miR-30c-2-3p and miR-339-5p function as tumor suppressors by targeting Rho GTPase activating protein 11A, 50 and BCL6. 51 However, repression of miR-151-5p inhibits cell proliferation in LC.…”

Section: Mirna-gene Networkmentioning

confidence: 99%

Sex differences in the tumor promoting effects of tobacco smoke in a cRaf transgenic lung cancer disease model

Zhong,

Borlak

2023

Preprint

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Background Tobacco smoke (TS) is the leading cause for lung cancer (LC), and female smokers are at a greater risk for LC. Yet, the underlying causes are unknown. Methods We performed whole genome scans in TS exposed wild type and histologically characterized tumor lesions of cRaf transgenic mice. We constructed miRNA-gene and transcription factor-miRNA/gene regulatory networks and determined sex-specific gene regulations by evaluating hormone receptor activities. We validated the findings from TS exposed cRaf mice in a large cohort of smoking and never-smoking LC patients Results When compared to males, TS prompted a 7-fold increase in tumor multiplicity in cRaf females. Genome-wide scans of tumor lesions identified 161 and 53 genes and miRNAs, which code for EGFR/MAPK signaling, cell proliferation, oncomirs and oncogenes, and 50% of DEGs coded for immune response and tumor evasion. Outstandingly, in transgenic males, TS elicited upregulation of 20 tumor suppressors, some of which are the targets of the androgen and estrogen receptor. Conversely, in females, 18 tumor suppressors were down-regulated, and five were specifically repressed by the estrogen receptor. We found TS to perturb the circadian clock in a sex-specific manner and identified a female-specific regulatory loop that consisted of the estrogen receptor, miR-22-3p and circadian genes to support LC growth. Finally, we confirmed sex dependent tumor promoting effects of TS in a large cohort of LC patients. Conclusions Our study highlights the sex-dependent genomic responses to TS and the interplay of circadian clock genes and hormone receptors in the regulation of oncogenes and oncomirs in LC growth.

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TEAD4 Activates PCSK9 to Promote Stomach Adenocarcinoma Cell Stemness through Fatty Acid Metabolism

Xu,

Han,

Zhou

et al. 2024

Digestion

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Introduction: This study attempted to investigate how PCSK9 influences the stemness of stomach adenocarcinoma (STAD) cells. Methods: CCK-8 and sphere formation assays were used to detect cell viability and stemness. qRT-PCR and western blot were used to detect PCSK9 and TEAD4 expression. The binding relationship was verified by dual luciferase and chromatin immunoprecipitation (ChIP) assays. The effect of TEAD4 activating PCSK9 on the stemness of STAD cells was detected by bioinformatics, BODIPY 493/503, Oil red O, western blot, and kits. In vivo experiments verified the role of the TEAD4/PCSK9 axis in tumor formation in nude mice. Results: PCSK9 and TEAD4 were highly expressed in STAD. PCSK9 was enriched in the FAM pathway. PCSK9 activated the fatty acid metabolism and promoted the proliferation and stemness of STAD cells. TEAD4 as a transcription factor upstream of PCSK9.Cell experiments revealed that knockdown of PCSK9 inhibited STAD cell stemness, whereas further addition of fatty acid inhibitors could attenuate the promoting effect on STAD cell stemness brought by STAD overexpression. Rescue experiments showed overexpressed PCSK9 exerted an inhibitory effect on the stemness of STAD cells brought by TEAD4 knockdown. The hypothesis that TEAD4/PCSK9 axis can promote STAD cell growth was confirmed by in vivo experiments. Conclusion: Transcription factor TEAD4 could activate PCSK9 to promote the stemness of STAD cells through FAM. These results added weight to the assumption that TEAD4/PCSK9 axis has the potential to be the therapeutic target that inhibits CSC in STAD.

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MicroRNA-30c-2-3p represses malignant progression of gastric adenocarcinoma cells via targeting ARHGAP11A

Cited by 4 publications

References 35 publications

Sex differences in the tumor promoting effects of tobacco smoke in a cRaf transgenic lung cancer disease model

Sex differences in the tumor promoting effects of tobacco smoke in a cRaf transgenic lung cancer disease model

Sex differences in the tumor promoting effects of tobacco smoke in a cRaf transgenic lung cancer disease model

TEAD4 Activates PCSK9 to Promote Stomach Adenocarcinoma Cell Stemness through Fatty Acid Metabolism

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