LIN28B Enhanced STAT3 Signaling Regulates Inflammatory Response and Chemotherapeutic Resistance in Cholangiocytes
| Autor: | Pattarin Nuwongsri, Nattapong Puthdee, Supaporn Khramchantuk |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
STAT3 Transcription Factor
Cell Survival medicine.medical_treatment Inflammation Cholangiocyte Cholangiocarcinoma Cancer stem cell Cell Line Tumor medicine Humans MTT assay Viability assay STAT3 biology Chemistry RNA-Binding Proteins Oncogenes General Medicine Gene Expression Regulation Neoplastic Cytokine Bile Duct Neoplasms Drug Resistance Neoplasm biology.protein Cancer research Cytokines Tumor necrosis factor alpha Bile Ducts Drug Screening Assays Antitumor medicine.symptom Signal Transduction |
| Zdroj: | Asian Pacific Journal of Cancer Prevention. 22:3671-3678 |
| ISSN: | 2476-762X |
| Popis: | Background LIN28B is functionally driving malignant transformation and relevance to the worse disease outcomes by promoting cancer aggressiveness. However, a typical role of LIN28B in cholangiocarcinoma (CCA) is primarily unknown. In this study, the tumorigenic potential of LIN28B in the cholangiocyte context was investigated. Methods Stable LIN28B expression in MMNK-1 cells was generated by infecting with retrovirus-containing LIN28B gene. LIN28B-overexpressing cells were further validated the amount of released cytokines by using human cytokine arrays. After treatment of chemo-drugs, cell viability was subsequently measured using MTT assay. Aldehyde dehydrogenase (ALDH) activity was determined using ALDEFLUOR assay Kit and analyzed by flow cytometry. The mRNA and protein expression levels were respectively assayed by RT-qPCR and western blot. Results Cytokine release results showed that numerous inflammatory cytokines-chemokines related to cancer initiation and development, such as IL-8, IL-6, VEGF, MCP1, TNF-α were significantly increased in LIN28B-overexpressing MMNK-1 cells. Drug sensitivity test showed that LIN28B-overexpressing MMNK-1 treated cells had a high percentage of cell viability compared to MMNK-1-control treated cells. Activity and expression level of a cancer stem cell marker, ALDH was significantly elevated in LIN28B-overexpressing MMNK-1 cells. Moreover, the activation of an oncogenic signaling pathway, signal transducer and activator of transcription 3 (STAT3) was enhanced in LIN28B-overexpressing MMNK-1 cells. Whereas, growth capacity of LIN28B-overexpressing MMNK-1 cells was found to be reduced in STAT3 inhibition. Conclusion LIN28B can regulate the inflammatory response and resistance to chemotherapy of cholangiocytes through modulation of STAT3 signaling pathway.A recent study suggests that activated cholangiocytes can be induced by regulation of LIN28B/STAT3 pathway and this may partially contribute to the initiating CCA. Here, LIN28B and its downstream signaling could be considered as an attractive therapeutic target in patients with CCA. |
| Databáze: | OpenAIRE |
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