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1.
Bone ; 181: 117038, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38316337

RESUMO

Osteoblast polarity, proliferation, differentiation, and migration are essential for maintaining normal bone structure and function. While the microtubule-associated protein Map1b has been extensively studied in nerve cells, its role in bone cells is less known. We investigated the functional significance of Map1b in mouse bone marrow stromal cells (ST2) and elucidated its relationship and influence on cytoskeletal polarity and Golgi organization. Our results suggest that Map1b, as a microtubule regulatory protein, can also regulate the expression of cyclin PCNA, p-H3(S10) and migration-related protein integrin ß1, thereby affecting the proliferation and migration of osteoblasts. The downstream target gene Rgc32 was screened by RNA sequencing. Furthermore, Map1b, as a downstream mediator, regulates the Wnt5a signaling pathway. This study expands our understanding of the involvement of Map1b in bone biology and highlights its crucial role in governing osteoblast polarity, proliferation, and migration, thereby providing a basis for developing novel therapeutic strategies targeting Map1b in orthopedic medicine and promoting precision treatment modalities. Further investigations on the precise mechanisms underlying Map1b's influence on bone cell function and disease progression are needed.


Assuntos
Osso e Ossos , Proteínas Associadas aos Microtúbulos , Camundongos , Animais , Proteínas Associadas aos Microtúbulos/metabolismo , Diferenciação Celular , Osso e Ossos/metabolismo , Osteoblastos/metabolismo , Proliferação de Células
2.
J Adv Res ; 54: 147-179, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-36736694

RESUMO

BACKGROUND: Tripartite motif (TRIM) family proteins have more than 80 members and are widely found in various eukaryotic cells. Most TRIM family proteins participate in the ubiquitin-proteasome degradation system as E3-ubiquitin ligases; therefore, they play pivotal regulatory roles in the occurrence and development of tumors, including tumor immune escape. Due to the diversity of functional domains of TRIM family proteins, they can extensively participate in multiple signaling pathways of tumor immune escape through different substrates. In current research and clinical contexts, immune escape has become an urgent problem. The extensive participation of TRIM family proteins in curing tumors or preventing postoperative recurrence and metastasis makes them promising targets. AIM OF REVIEW: The aim of the review is to make up for the gap in the current research on TRIM family proteins and tumor immune escape and propose future development directions according to the current progress and problems. KEY SCIENTIFIC CONCEPTS OF REVIEW: This up-to-date review summarizes the characteristics and biological functions of TRIM family proteins, discusses the mechanisms of TRIM family proteins involved in tumor immune escape, and highlights the specific mechanism from the level of structure-function-molecule-pathway-phenotype, including mechanisms at the level of protein domains and functions, at the level of molecules and signaling pathways, and at the level of cells and microenvironments. We also discuss the application potential of TRIM family proteins in tumor immunotherapy, such as possible treatment strategies for combination targeting TRIM family protein drugs and checkpoint inhibitors for improving cancer treatment.


Assuntos
Neoplasias , Evasão Tumoral , Humanos , Proteínas com Motivo Tripartido/química , Proteínas com Motivo Tripartido/genética , Proteínas com Motivo Tripartido/metabolismo , Ubiquitina/metabolismo , Ubiquitina-Proteína Ligases/metabolismo , Microambiente Tumoral
3.
Stem Cell Res Ther ; 13(1): 521, 2022 11 22.
Artigo em Inglês | MEDLINE | ID: mdl-36414991

RESUMO

MicroRNAs (miRNAs) are non-coding single-stranded RNA molecules encoded by endogenous genes, which play a vital role in cell generation, metabolism, apoptosis and stem cell differentiation. C3H10T1/2, a mesenchymal cell extracted from mouse embryos, is capable of osteogenic differentiation, adipogenic differentiation and chondrogenic differentiation. Extensive studies have shown that not only miRNAs can directly trigger targeted genes to regulate the tri-lineage differentiation of C3H10T1/2, but it also can indirectly regulate the differentiation by triggering different signaling pathways or various downstream molecules. This paper aims to clarify the regulatory roles of different miRNAs on C3H10T1/2 differentiation, and discussing their balance effect among osteogenic differentiation, adipogenic differentiation and chondrogenic differentiation of C3H10T1/2. We also review the biogenesis of miRNAs, Wnt signaling pathways, MAPK signaling pathways and BMP signaling pathways and provide some specific examples of how these signaling pathways act on C3H10T1/2 tri-lineage differentiation. On this basis, we hope that a deeper understanding of the differentiation and regulation mechanism of miRNAs in C3H10T1/2 can provide a promising therapeutic method for the clinical treatment of bone defects, osteoporosis, osteoarthritis and other diseases.


Assuntos
MicroRNAs , Animais , Camundongos , MicroRNAs/genética , Osteogênese/genética , Diferenciação Celular/genética , Condrogênese/genética , Adipogenia/genética
4.
Cell Death Discov ; 8(1): 262, 2022 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-35577802

RESUMO

MicroRNAs(miRNAs) are non-coding single-stranded RNA molecules encoded by endogenous genes with a length of about 22 nucleotides. The dysregulation of miRNAs has been proven to be one of the vital causes of cancer, which makes them a biomarker for cancer diagnosis and prognosis. Compared with surgery and chemotherapy, nucleic acid therapy targeting specific miRNAs is a promising candidate for cancer treatment. miR-20a-5p plays an anticancer role in high-incidence human cancers such as cervical cancer, breast cancer and leukemia, which is of great importance in the diagnosis of cancers. The up-regulation and down-regulation of miR-20a-5p offers a possible breakthrough for the treatment of cancers. In this paper, we aim to investigate the functional significance of miR-20a-5p in different cancers, reviewing the expression differences of miR-20a-5p in cancer, while systematically summarizing the changes of circRNA-miR-20a-5p networks, and probe how it promotes messenger RNA (mRNA) degradation or inhibits mRNA translation to regulate downstream gene expression. We've also summarized the biogenesis mechanism of miRNAs, and emphasized its role in cell proliferation, cell apoptosis and cell migration. On this basis, we believe that miR-20a-5p is a promising and effective marker for cancer diagnosis, prognosis and treatment.

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