Open AccessA positive feedback loop between miR‐181b and STAT 3 that affects Warburg effect in colon cancer via regulating PIAS 3 expression
Author(s) -
Pan Xiaolin,
Feng Jin,
Zhu Zhenhua,
Yao Linhua,
Ma Shijie,
Hao Bo,
Zhang Guoxin
Publication year - 2018
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.13786
Subject(s) - colorectal cancer , cancer research , stat , western blot , warburg effect , medicine , chemistry , cancer , biology , cancer cell , phosphorylation , stat3 , microbiology and biotechnology , biochemistry , gene
This study aimed to investigate the relationship between the expression of micro RNA (miR)‐181b, protein inhibitor of activated STAT 3 ( PIAS 3) and STAT 3, and to examine the function of the miR‐181b/ PIAS 3/ STAT 3 axis on the Warburg effect and xenograft tumour growth of colon cancer. Moreover, a positive feedback loop between miR‐181b and STAT 3 that regulated the Warburg effect in colon cancer was explored. A luciferase reporter assay was used to identify whether PIAS 3 was a direct target of miR‐181b. The gain‐of‐function and loss‐of‐function experiments were performed on HCT 116 cells to investigate the effect of miR‐181b/ PIAS 3/ STAT 3 on the Warburg effect and xenograft tumour growth of colon cancer, as determined by commercial kits and xenograft experiments. The relationship between the expression of miR‐181b, PIAS 3 and STAT 3 in HCT 116 and HT ‐29 cells was determined using RT ‐ qPCR and Western blot. We found miR‐181b was a direct regulator of PIAS 3. miR‐181b promoted the Warburg effect and the growth of colon cancer xenografts; however, these effects could be reversed by PIAS 3. miR‐181b expression interacted with STAT 3 phosphorylation in a positive feedback loop in colon cancer cells via regulating PIAS 3 expression. In conclusion, this study for the first time demonstrated that miR‐181b contributed to the Warburg effect and xenograft tumour growth of colon cancer by targeting PIAS 3. Moreover, a positive feedback loop between miR‐181b and STAT 3 that regulated the Warburg effect in colon cancer was also demonstrated. This study suggested miR‐181b/ PIAS 3/ STAT 3 axis as a novel target for colon cancer treatment.