PMID- 34837926
OWN - NLM
STAT- MEDLINE
DCOM- 20220210
LR  - 20220716
IS  - 2476-762X (Electronic)
IS  - 1513-7368 (Print)
IS  - 1513-7368 (Linking)
VI  - 22
IP  - 11
DP  - 2021 Nov 1
TI  - LIN28B Enhanced STAT3 Signaling Regulates Inflammatory Response and 
      Chemotherapeutic Resistance in Cholangiocytes.
PG  - 3671-3678
LID - 89856 [pii]
LID - 10.31557/APJCP.2021.22.11.3671 [doi]
AB  - 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-alpha 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.
FAU - Puthdee, Nattapong
AU  - Puthdee N
AUID- ORCID: 0000-0002-8503-4271
AD  - Department of Biochemistry, Faculty of Medicine, Chulalongkorn University, 
      Bangkok, Thailand.
FAU - Khramchantuk, Supaporn
AU  - Khramchantuk S
AD  - Excellence Center for Stem Cell and Cell Therapy, King Chulalongkorn Memorial 
      Hospital, the Thai Red Cross Society, Bangkok, Thailand.
FAU - Nuwongsri, Pattarin
AU  - Nuwongsri P
AD  - Graduate School, Faculty of Medicine, Chulalongkorn University, Bangkok, 
      Thailand.
LA  - eng
PT  - Journal Article
DEP - 20211101
PL  - Thailand
TA  - Asian Pac J Cancer Prev
JT  - Asian Pacific journal of cancer prevention : APJCP
JID - 101130625
RN  - 0 (Cytokines)
RN  - 0 (LIN28B protein, human)
RN  - 0 (RNA-Binding Proteins)
RN  - 0 (STAT3 Transcription Factor)
RN  - 0 (STAT3 protein, human)
SB  - IM
MH  - Bile Duct Neoplasms/*genetics
MH  - Bile Ducts/cytology
MH  - Cell Line, Tumor
MH  - Cell Survival/genetics
MH  - Cholangiocarcinoma/*genetics
MH  - Cytokines/metabolism
MH  - Drug Resistance, Neoplasm/*genetics
MH  - Drug Screening Assays, Antitumor
MH  - Gene Expression Regulation, Neoplastic/genetics
MH  - Humans
MH  - Oncogenes/genetics
MH  - RNA-Binding Proteins/*physiology
MH  - STAT3 Transcription Factor/*metabolism
MH  - Signal Transduction/genetics
PMC - PMC9068185
OTO - NOTNLM
OT  - Bile duct cancer
OT  - Inflammation
OT  - RNA-binding protein
OT  - drugs resistance
OT  - tumor-initiation
EDAT- 2021/11/29 06:00
MHDA- 2022/02/11 06:00
PMCR- 2022/01/01
CRDT- 2021/11/28 17:37
PHST- 2021/08/09 00:00 [received]
PHST- 2021/11/28 17:37 [entrez]
PHST- 2021/11/29 06:00 [pubmed]
PHST- 2022/02/11 06:00 [medline]
PHST- 2022/01/01 00:00 [pmc-release]
AID - 89856 [pii]
AID - 10.31557/APJCP.2021.22.11.3671 [doi]
PST - epublish
SO  - Asian Pac J Cancer Prev. 2021 Nov 1;22(11):3671-3678. doi: 
      10.31557/APJCP.2021.22.11.3671.