Dynamical modeling of miR-34a, miR-449a, and miR-16 reveals numerous DDR signaling pathways regulating senescence, autophagy, and apoptosis in HeLa cells

Autor(es)

Gupta, Shantanu ; Panda, Pritam Kumar ; Hashimoto, Ronaldo F. ; Samal, Shailesh Kumar ; Mishra, Suman ; Verma, Suresh Kr ; Mishra, Yogendra Kumar ; Ahuja, Rajeev

• Tipo de documento: Artigo Científico
• Fonte: SCIENTIFIC REPORTS; v. 12, n. 1, p. 13-pg., 2022-03-22.

Resumo

Transfection of tumor suppressor miRNAs such as miR-34a, miR-449a, and miR-16 with DNA damage can regulate apoptosis and senescence in cancer cells. miR-16 has been shown to influence autophagy in cervical cancer. However, the function of miR-34a and miR-449a in autophagy remains unknown. The functional and persistent G1/S checkpoint signaling pathways in HeLa cells via these three miRNAs, either synergistically or separately, remain a mystery. As a result, we present a synthetic Boolean network of the functional G1/S checkpoint regulation, illustrating the regulatory effects of these three miRNAs. To our knowledge, this is the first synthetic Boolean network that demonstrates the advanced role of these miRNAs in cervical cancer signaling pathways reliant on or independent of p53, such as MAPK or AMPK. We compared our estimated probability to the experimental data and found reasonable agreement. Our findings indicate that miR-34a or miR-16 may control senescence, autophagy, apoptosis, and the functional G1/S checkpoint. Additionally, miR-449a can regulate just senescence and apoptosis on an individual basis. MiR-449a can coordinate autophagy in HeLa cells in a synergistic manner with miR-16 and/or miR-34a. (AU)

• Processo FAPESP: 21/09070-8 - Modelagem, análise e inferência de redes biológicas
• Beneficiário: Shantanu Gupta
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado
• Processo FAPESP: 15/22308-2 - Representações intermediárias em Ciência Computacional para descoberta de conhecimento
• Beneficiário: Roberto Marcondes Cesar Junior
• Modalidade de apoio: Auxílio à Pesquisa - Temático