miR-509-5p Inhibits the Proliferation and Invasion of Osteosarcoma by Targeting TRIB2

Guo, Jiekun; Wu, Qiang; Peng, Xiaoming; Yu, Bin

doi:10.1155/2019/2523032

Cited by 11 publications

(7 citation statements)

References 26 publications

(23 reference statements)

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“…This study shows that miR-206 and miR-140 target the transcription factor phospho-Smad3 which, in turn, binds CAGACA sequences in TRIB2 promoter. In line with this data, in osteosarcoma tissues and cell lines, TRIB2 is a direct target of miR-509-5p and when miR-509-5p is overexpressed or TRIB2 is silenced, the malignant capacity of osteosarcoma cells, in terms of proliferation and invasion, its reduced [ 103 ]. Additionally, TRIB2 stability could be target by modifying Ubiquitin E3 ligase SCF β-TRCP levels.…”

Section: Targeting Trib2mentioning

confidence: 86%

The Critical Role of TRIB2 in Cancer and Therapy Resistance

Mayoral-Varo

Jiménez

Link

2021

Cancers

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The Tribbles pseudokinases family consists of TRIB1, TRIB2, TRIB3 and STK40 and, although evolutionarily conserved, they have distinctive characteristics. Tribbles members are expressed in a context and cell compartment-dependent manner. For example, TRIB1 and TRIB2 have potent oncogenic activities in vertebrate cells. Since the identification of Tribbles proteins as modulators of multiple signalling pathways, recent studies have linked their expression with several pathologies, including cancer. Tribbles proteins act as protein adaptors involved in the ubiquitin-proteasome degradation system, as they bridge the gap between substrates and E3 ligases. Between TRIB family members, TRIB2 is the most ancestral member of the family. TRIB2 is involved in protein homeostasis regulation of C/EBPα, β-catenin and TCF4. On the other hand, TRIB2 interacts with MAPKK, AKT and NFkB proteins, involved in cell survival, proliferation and immune response. Here, we review the characteristic features of TRIB2 structure and signalling and its role in many cancer subtypes with an emphasis on TRIB2 function in therapy resistance in melanoma, leukemia and glioblastoma. The strong evidence between TRIB2 expression and chemoresistance provides an attractive opportunity for targeting TRIB2.

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Section: Targeting Trib2mentioning

confidence: 86%

The Critical Role of TRIB2 in Cancer and Therapy Resistance

Mayoral-Varo

Jiménez

Link

2021

Cancers

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“…Also, miR-509 as epithelial-mesenchymal transition miRNA was shown to induce the expression of E-cadherin, and inhibit cell motility and invasion 52 . In addition, miR-509 can inhibit cell motility and invasion through targeting tribbles pseudokinase 2 ( TRIB2) in osteosarcoma 53 . Our findings showed that miR-509 was significantly down-regulated in tumor tissues in comparison with their adjacent non-tumoral tissues, and lower miR-509 expression in tumoral tissues was associated with high tumor grade, stage, and H. pylori infection.…”

Section: Resultsmentioning

confidence: 99%

Association of sonic hedgehog signaling pathway genes IHH, BOC, RAB23a and MIR195-5p, MIR509-3-5p, MIR6738-3p with gastric cancer stage

Fattahi

Nikbakhsh

Ranaei

et al. 2021

Sci Rep

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Gastric cancer is the leading cause of cancer-related mortality worldwide. Given the importance of gastric cancer in public health, identifying biomarkers associated with disease onset is an important part of precision medicine. The hedgehog signaling pathway is considered as one of the most significant widespread pathways of intracellular signaling in the early events of embryonic development. This pathway contributes also to the maintenance of pluripotency of cancer stem cells pluripotency. In this study, we analyzed the expression levels of sonic hedgehog (Shh) signaling pathway genes IHH, BOC, RAB23a and their regulatory miRNAs including MIR-195-5p, MIR-509-3-5p, MIR-6738-3p in gastric cancer patients. In addition, the impact of infection status on the expression level of those genes and their regulatory miRNAs was investigated. One hundred samples taken from 50 gastric cancer patients (50 tumoral tissues and their adjacent non-tumoral counterparts) were included in this study. There was a significant difference in all studied genes and miRNAs in tumoral tissues in comparison with their adjacent non-tumoral counterparts. The lower expression of IHH, BOC, RAB23, miR-195-5p, and miR-6738-3p was significantly associated with more advanced cancer stage. Additionally, IHH upregulation was significantly associated with CMV infection (P < 0.001). Also, receiver operating characteristic (ROC) curve analysis indicated that mir-195 was significantly related to several clinicopathological features including tumor stage, grade, age, gender, and infection status of gastric cancer and can be considered as a potential diagnostic biomarker for gastric cancer. This study confirms the important role of Shh signaling pathway genes in gastric cancer tumorigenesis and their potential as novel molecular biomarkers and therapeutic targets.

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“…Trib2 is a cancer-associated pseudokinase that can be induced by mitogens and enhances the propagation of several cancer cells, including myeloid leukemia, liver, lung, skin, bone, brain, and pancreatic [ 10 , 46 ] (Table 1 ).…”

Section: Different Roles Of Trib2 In Tumorigenesismentioning

confidence: 99%

Tribbles homolog 2 (Trib2), a pseudo serine/threonine kinase in tumorigenesis and stem cell fate decisions

Zekiy

Ghaedrahmati

et al. 2021

Cell Commun Signal

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The family of Tribbles proteins play many critical nonenzymatic roles and regulate a wide range of key signaling pathways. Tribbles homolog 2 (Trib2) is a pseudo serine/threonine kinase that functions as a scaffold or adaptor in various physiological and pathological processes. Trib2 can interact with E3 ubiquitin ligases and control protein stability of downstream effectors. This protein is induced by mitogens and enhances the propagation of several cancer cells, including myeloid leukemia, liver, lung, skin, bone, brain, and pancreatic. Thus, Trib2 can be a predictive and valuable biomarker for the diagnosis and treatment of cancer. Recent studies have illustrated that Trib2 plays a major role in cell fate determination of stem cells. Stem cells have the capacity to self-renew and differentiate into specific cell types. Stem cells are important sources for cell-based regenerative medicine and drug screening. Trib2 has been found to increase the self-renewal ability of embryonic stem cells, the reprogramming efficiency of somatic cells, and chondrogenesis. In this review, we will focus on the recent advances of Trib2 function in tumorigenesis and stem cell fate decisions.

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miR-509-5p Inhibits the Proliferation and Invasion of Osteosarcoma by Targeting TRIB2

Cited by 11 publications

References 26 publications

The Critical Role of TRIB2 in Cancer and Therapy Resistance

The Critical Role of TRIB2 in Cancer and Therapy Resistance

Association of sonic hedgehog signaling pathway genes IHH, BOC, RAB23a and MIR195-5p, MIR509-3-5p, MIR6738-3p with gastric cancer stage

Tribbles homolog 2 (Trib2), a pseudo serine/threonine kinase in tumorigenesis and stem cell fate decisions

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