MicroRNA-106a regulates autophagy-related cell death and EMT by targeting TP53INP1 in lung cancer with bone metastasis

Han, Lei; Huang, Zeyong; Liu, Yan; Yang, Lijuan; Li, Dongqi; Yao, Zhihong; Wang, Cao; Zhang, Ya; Yang, Hang; Tan, Zunxian; Tang, Jiadai; Yang, Zuozhang

doi:10.1038/s41419-021-04324-0

Cited by 30 publications

(18 citation statements)

References 56 publications

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“…In addition, numerous genes identified as being associated with the cross-trait shared architecture of T2D and PAD in Europeans have similar functions to those in East Asians. For example, TP53INP1 (European-specific) and MOB1B (East Asian-specific) both have functions related to cell migration and death [ 103 , 104 ]; CHMP4B (European-specific) and AP3S2 (East Asian-specific) are involved in protein transport and intracellular trafficking [ 105 , 106 ]. These genes were reported as harboring SNPs significantly associated with T2D [ 1 , 107 , 108 ].…”

Section: Discussionmentioning

confidence: 99%

Genetic evidence for a causal relationship between type 2 diabetes and peripheral artery disease in both Europeans and East Asians

Xiu

Zhang

Xue

et al. 2022

BMC Med

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Background Observational studies have revealed that type 2 diabetes (T2D) is associated with an increased risk of peripheral artery disease (PAD). However, whether the two diseases share a genetic basis and whether the relationship is causal remain unclear. It is also unclear as to whether these relationships differ between ethnic groups. Methods By leveraging large-scale genome-wide association study (GWAS) summary statistics of T2D (European-based: Ncase = 21,926, Ncontrol = 342,747; East Asian-based: Ncase = 36,614, Ncontrol = 155,150) and PAD (European-based: Ncase = 5673, Ncontrol = 359,551; East Asian-based: Ncase = 3593, Ncontrol = 208,860), we explored the genetic correlation and putative causal relationship between T2D and PAD in both Europeans and East Asians using linkage disequilibrium score regression and seven Mendelian randomization (MR) models. We also performed multi-trait analysis of GWAS and two gene-based analyses to reveal candidate variants and risk genes involved in the shared genetic basis between T2D and PAD. Results We observed a strong genetic correlation (rg) between T2D and PAD in both Europeans (rg = 0.51; p-value = 9.34 × 10−15) and East Asians (rg = 0.46; p-value = 1.67 × 10−12). The MR analyses provided consistent evidence for a causal effect of T2D on PAD in both ethnicities (odds ratio [OR] = 1.05 to 1.28 for Europeans and 1.15 to 1.27 for East Asians) but not PAD on T2D. This putative causal effect was not influenced by total cholesterol, body mass index, systolic blood pressure, or smoking initiation according to multivariable MR analysis, and the genetic overlap between T2D and PAD was further explored employing an independent European sample through polygenic risk score regression. Multi-trait analysis of GWAS revealed two novel European-specific single nucleotide polymorphisms (rs927742 and rs1734409) associated with the shared genetic basis of T2D and PAD. Gene-based analyses consistently identified one gene ANKFY1 and gene-gene interactions (e.g., STARD10 [European-specific] to AP3S2 [East Asian-specific]; KCNJ11 [European-specific] to KCNQ1 [East Asian-specific]) associated with the trans-ethnic genetic overlap between T2D and PAD, reflecting a common genetic basis for the co-occurrence of T2D and PAD in both Europeans and East Asians. Conclusions Our study provides the first evidence for a genetically causal effect of T2D on PAD in both Europeans and East Asians. Several candidate variants and risk genes were identified as being associated with this genetic overlap. Our findings emphasize the importance of monitoring PAD status in T2D patients and suggest new genetic biomarkers for screening PAD risk among patients with T2D.

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Section: Discussionmentioning

confidence: 99%

Genetic evidence for a causal relationship between type 2 diabetes and peripheral artery disease in both Europeans and East Asians

Xiu

Zhang

Xue

et al. 2022

BMC Med

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“…MicroRNA is a non-coding RNA of about 22 nucleotides in length.It was rst thought to bind to the 3' UTR of gene mRNA by incomplete complementation, inhibiting protein translation, thereby inhibiting protein synthesis and blocking the translation process of mRNA.Typically, miRNAs negatively regulate target genes and can degrade mRNA or inhibit translation.At the same time, MicroRNAs also play an important role in the occurrence and development of tumors.For instance,microRNA-106a regulates autophagyrelated cell death and EMT by targeting TP53INP1 in lung cancer with bone metastasis [43].Tumor-derived exosomal miR-934 induces macrophage M2 polarization to promote liver metastasis of colorectal cancer [44].Studies have shown that circRNA may have a base sequence that binds to miRNA, which can act as a competitive endogenous RNA to competitively bind to miRNA, relieve the inhibitory effect of miRNA on target genes, and then affect the occurrence and development of tumors [45].Circ-ZEB1 promotes PIK3CA expression by silencing miR-199a-3p and affects the proliferation and apoptosis of hepatocellular carcinoma [46].Our previous experiments found that hsa_circ_0021727 could act as a "molecular sponge" for miR-23b-5p.MiR-23b-5p was shown to be an important regulatory molecule in tumorigenesis and development.Dysregulation of miR-23b-5p promotes cell proliferation via targeting FOXM1 in hepatocellular carcinoma [47].MiR-23b-5p promotes the chemosensitivity of temozolomide via negatively regulating TLR4 in glioma [48].In our experiments, miR-23b-5p played an important role as a tumor suppressor.It can reduce the translation of the downstream target gene TAB1, thereby inactivating the NFκB pathway.…”

Section: Discussionmentioning

confidence: 99%

Hsa_circ_0021727 (circ-CD44) promotes ESCC progression by targeting miR-23b-5p to activate the TAB1/NFκB pathway

Meng

Zhang

Wang

et al. 2022

Preprint

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Background: The morbidity and mortality of esophageal squamous cell carcinoma (ESCC) remain high globally. Circular RNAs (circRNAs) play an important role in tumor progression. We discovered a novel aberrantly expressed circRNA (hsa_circ_0021727) in ESCC patients. However, the mechanism of hsa_circ_0021727 in tumors is still not elucidated. The purpose of this article is to investigate the biological role of hsa_circ_0021727 and its role in ESCC progression.Methods: Microarray analysis was used to screen diferentially expressed novel circRNAs.qRT-PCR,RNA-ISH and FISH were used to analyze the expression and localization of hsa_circ_0021727.MTT, colony formation, EdU, transwell assay, three-dimensional (3D) spheroid invasion assays and wound healing assays were used to describe biological effects on ESCC cells.Xenograft experiment and tail vein injection experiment were used to analyze tumor growth and metastasis in vivo.RNA-sequencing was used to identify hsa_circ_0021727 downstream targets.Western blot was used to detect the downstream protein expression of hsa_circ_0021727.RNA pulldown and dual luciferase experiments were used to evaluate the interaction of hsa_circ_0021727, miR-23b-5p and TAB1.Results: We screened a novel circRNA (hsa_circ_0021727) whose expression was upregulated in ESCC patients.ESCC patients with high expression of hsa_circ_0021727 had shorter survival time.Hsa_circ_0021727 promoted the proliferation, invasion and migration of ESCC cells. However, miR-23b-5p inhibited this ability of hsa_circ_0021727. MiR-23b-5p acts by targeting TAB1. In conclusion, hsa_circ_0021727 promoted ESCC progression by upregulating the expression of TAK1-binding protein 1(TAB1) via "sponge adsorption" of miR-23b-5p. In addition, in vivo experiments also confirmed that hsa_circ_0021727 can promote the proliferation, invasion and migration of ESCC cells.Conclusions：Hsa_circ_0021727 (circ_CD44) promotes ESCC progression by targeting miR-23b-5p to activate the TAB1/NFκB pathway.These findings may provide potential targets for the treatment of ESCC.

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“…Wnt/β-catenin pathway [95] miR-106a miR-106a/TP53INP1 [96] miR-139-5p miR-139-5p/Notch 1 [97] miR-17-5p PTEN/PI3K/Akt [98] miR-365 NKX2-1/EGFR/PI3K [99] miR-192-5p miR-192-5p/ TRIM-44 [100] miR-886-3p miR-886-3p-PLK1/TGF-β1 pathway [101] DNA methylation DNMTs miR-886-3p-PLK1/TGF-β1 pathway [101] DNMTs WIF-1 [102] Prostate cancer ncRNA lncRNA NEAT1 CYCLINL1/CDK19/ NEAT1-1 [103] miR-940 miR-940/ARHGAP1 and FAM134A [104] miR-181b-5p miR-181b-5p/ Oncostatin M axis [105] lncRNA HOXA11-AS HOXB13/lncRNA HOXA11-AS/ IBSP [106] lncRNA PCAT6 PCAT6/IGF2BP2/IGF1R axis [107] lncRNA NEAT1 miR-205-5p/RUNX2/ SFPQ/PTBP2 axis [108] miR-378a-3p miR-378a-3p/ Dyrk1a/ Nfatc1/Angptl2 [109] Deciphering and Targeting Epigenetics in Cancer Metastasis DOI: http://dx.doi.org/10.5772/intechopen.106584…”

Section: Cancer Types Epigenetic Types Biomarkers Pathways Referencesmentioning

confidence: 99%

Deciphering and Targeting Epigenetics in Cancer Metastasis

Huang¹,

Lu²,

Liang³

2023

Cancer Metastasis - Molecular Mechanism and Clinical Therapy

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Once cancer metastasizes to distant organs like the bone, liver, lung, and brain, it is in an advanced stage. Metastasis is a major contributor to cancer-associated deaths. Countless molecules and complex pathways are involved in the dissemination and colonization of cancer cells from a primary tumor at metastatic sites. Establishing the biological mechanisms of the metastatic process is crucial in finding open therapeutic windows for successful interventions. Emerging evidence suggested a variety of epigenetic regulations were identified to regulate cancer metastasis. Here we summarize the procedures and routes of cancer metastasis as well as the roles of epigenetics including ncRNA, DNA methylation, and histone modifications in common metastases. Then we further discuss the potentials and limitations of epigenetics-related target molecules in diagnosis, therapy, and prognosis.

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MicroRNA-106a regulates autophagy-related cell death and EMT by targeting TP53INP1 in lung cancer with bone metastasis

Cited by 30 publications

References 56 publications

Genetic evidence for a causal relationship between type 2 diabetes and peripheral artery disease in both Europeans and East Asians

Genetic evidence for a causal relationship between type 2 diabetes and peripheral artery disease in both Europeans and East Asians

Hsa_circ_0021727 (circ-CD44) promotes ESCC progression by targeting miR-23b-5p to activate the TAB1/NFκB pathway

Deciphering and Targeting Epigenetics in Cancer Metastasis

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