The mir-133a, tpm4 and tap63γ role in myocyte differentiation microfilament remodelling and colon cancer progression

Autor: Sabrina Caporali, Stefano D'Ottavio, Massimo Pieri, Claudio Cortese, Sergio Bernardini, Alessandro Terrinoni, Silvia Angeletti, Marilena Minieri, Umberto Tarantino, Alessandro Mauriello, Cosimo Calabrese, Mario Marini
Jazyk: angličtina
Rok vydání: 2021
Předmět:
Carcinogenesis
MiR-133a
Tropomyosin
Microfilament
Muscle Development
Stress Fibers
Myocyte
Biology (General)
Cytoskeleton
Spectroscopy
Tropomyosins
Settore BIO/12
Cell Differentiation
General Medicine
Microfilament Protein
Computer Science Applications
Cell biology
Gene Expression Regulation
Neoplastic
Chemistry
Actin Cytoskeleton
medicine.anatomical_structure
colon carcinoma (CRC)
Colonic Neoplasms
MiRNAs
QH301-705.5
Biology
Article
Catalysis
Inorganic Chemistry
Downregulation and upregulation
Cell Line
Tumor
medicine
Humans
TAp63
Physical and Theoretical Chemistry
Muscle
Skeletal
QD1-999
Molecular Biology
Transcription factor
Cell Proliferation
Muscle Cells
Physical activity
Tumor Suppressor Proteins
Organic Chemistry
Skeletal muscle
Circulating miRs
Colon carcinoma (CRC)
TAp63
MicroRNAs
TPM4
Cancer cell
Transcription Factors
Zdroj: International Journal of Molecular Sciences
Volume 22
Issue 18
International Journal of Molecular Sciences, Vol 22, Iss 9818, p 9818 (2021)
Popis: MicroRNAs (miRNAs) play an essential role in the regulation of a number of physiological functions. miR-133a and other muscular miRs (myomiRs) play a key role in muscle cell growth and in some type of cancers. Here, we show that miR133a is upregulated in individuals that undertake physical exercise. We used a skeletal muscle differentiation model to dissect miR-133a’s role and to identify new targets, identifying Tropomyosin-4 (TPM4). This protein is expressed during muscle differentiation, but importantly it is an essential component of microfilament cytoskeleton and stress fibres formation. The microfilament scaffold remodelling is an essential step in cell transformation and tumour progression. Using the muscle system, we obtained valuable information about the microfilament proteins, and the knowledge on these molecular players can be transferred to the cytoskeleton rearrangement observed in cancer cells. Further investigations showed a role of TPM4 in cancer physiology, specifically, we found that miR-133a downregulation leads to TPM4 upregulation in colon carcinoma (CRC), and this correlates with a lower patient survival. At molecular level, we demonstrated in myocyte differentiation that TPM4 is positively regulated by the TA isoform of the p63 transcription factor. In muscles, miR-133a generates a myogenic stimulus, reducing the differentiation by downregulating TPM4. In this system, miR-133a counteracts the differentiative TAp63 activity. Interestingly, in CRC cell lines and in patient biopsies, miR-133a is able to regulate TPM4 activity, while TAp63 is not active. The downregulation of the miR leads to TPM4 overexpression, this modifies the architecture of the cell cytoskeleton contributing to increase the invasiveness of the tumour and associating with a poor prognosis. These results add data to the interesting question about the link between physical activity, muscle physiology and protection against colorectal cancer. The two phenomena have in common the cytoskeleton remodelling, due to the TPM4 activity, that is involved in stress fibres formation.
Databáze: OpenAIRE
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