PKM2 promotes glucose metabolism through a let‐7a‐5p/Stat3/hnRNP‐A1 regulatory feedback loop in breast cancer cells

Yao, Ao; Yuan, Xiang; Si, Yu-Rui; Fan, Lijuan; Li, Jiapeng; Li, Hui; Guo, Wei; He, Huixin; Liang, Xing‐Jie; Tan, Yao; Bao, Lidao; Liao, Xing–Hua

doi:10.1002/jcb.27947

Cited by 52 publications

(33 citation statements)

References 40 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The study by Lin et al [35] indicates that palmitic acid limits glycometabolism through the attenuation of STAT3 pathway in hepatocellular carcinoma. Furthermore, STAT3 signaling participates in the pyruvate kinase isoenzyme type M2-mediated glycolysis of breast cancer cells [36]. Our data herein suggested STAT3 played a crucial role in HK2 expression and glucose metabolism of human CRC cells.…”

Section: Discussionmentioning

confidence: 61%

Polo-like kinase 3 inhibits glucose metabolism in colorectal cancer by targeting HSP90/STAT3/HK2 signaling

Sun

Zhao

et al. 2019

J Exp Clin Cancer Res

View full text Add to dashboard Cite

BackgroundPolo-like kinase 3 (PLK3) has been documented as a tumor suppressor in several types of malignancies. However, the role of PLK3 in colorectal cancer (CRC) progression and glucose metabolism remains to be known.MethodsThe expression of PLK3 in CRC tissues was determined by immunohistochemistry. Cells proliferation was examined by EdU, CCK-8 and in vivo analyses. Glucose metabolism was assessed by detecting lactate production, glucose uptake, mitochondrial respiration, extracellular acidification rate, oxygen consumption rate and ATP production. Chromatin immunoprecipitation, luciferase reporter assays and co-immunoprecipitation were performed to explore the signaling pathway. Specific targeting by miRNAs was determined by luciferase reporter assays and correlation with target protein expression.ResultsPLK3 was significantly downregulated in CRC tissues and its low expression was correlated with worse prognosis of patients. In vitro and in vivo experiments revealed that PLK3 contributed to growth inhibition of CRC cells. Furthermore, we demonstrated that PLK3 impeded glucose metabolism via targeting Hexokinase 2 (HK2) expression. Mechanically, PLK3 bound to Heat shock protein 90 (HSP90) and facilitated its degradation, which led to a significant decrease of phosphorylated STAT3. The downregulation of p-STAT3 further suppressed the transcriptional activation of HK2. Moreover, our investigations showed that PLK3 was directly targeted by miR-106b at post-transcriptional level in CRC cells.ConclusionThis study suggests that PLK3 inhibits glucose metabolism by targeting HSP90/STAT3/HK2 signaling and PLK3 may serve as a potential therapeutic target in colorectal cancer.

show abstract

Section: Discussionmentioning

confidence: 61%

Polo-like kinase 3 inhibits glucose metabolism in colorectal cancer by targeting HSP90/STAT3/HK2 signaling

Sun

Zhao

et al. 2019

J Exp Clin Cancer Res

View full text Add to dashboard Cite

show abstract

“…There is growing evidence that miRNAs can regulate glycolysis directly by regulating the expression of genes encoding for glycolysis pathway or indirectly by controlling the expression of oncogenes and tumor suppressor genes involved in glycolysis. Hsa-let-7a has been shown to regulate glycolysis in various cancers [70–72]. In addition, SIRT2, which was downregulated by hsa-miRNA-1972 has been shown to be a potent regulator of glycolysis [73].…”

Section: Discussionmentioning

confidence: 99%

Role of miRNA in the regulation of cannabidiol-mediated apoptosis in neuroblastoma cells

2019

View full text Add to dashboard Cite

Neuroblastoma (NBL) is one of the most common childhood cancers that originate from the immature nerve cells of the sympathetic system. Studies with NBL cancers have also shown that miRNAs are dysregulated and may play a critical role in pathogenesis. Cannabidiol (CBD) is a non-psychoactive compound found in marijuana which has been previously shown by our laboratory and others to induce apoptosis in cancer cells. However, there are no studies reported to test if CBD mediates these effects through regulation of miRNA. In the current study, therefore, we investigated if CBD induces apoptosis in human NBL cell lines, SH SY5Y and IMR-32, and if it is regulated by miRNA. Our data demonstrated that CBD induces apoptosis in NBL cells through activation of serotonin and vanilloid receptors. We also found that caspase-2 and -3 played an important role in the induction of apoptosis. CBD also significantly reduced NBL cell migration and invasion in vitro. Furthermore, CBD blocked mitochondrial respiration and caused a shift in metabolism towards glycolysis. CBD altered the expression of miRNA specifically, down-regulating hsa-let-7a and upregulating hsa-mir-1972. Downregulation of let-7a increased expression of target caspase-3, and growth arrest specific-7 (GAS-7) genes. Upregulation of hsa-mir-1972 caused decreased expression of BCL2L1 and SIRT2 genes. Together, our studies suggest that CBD-mediated apoptosis in NBL cells is regulated by miRNA.

show abstract

“…Since the discovery of Warburg effects, metabolism is strongly linked with proliferation of cancer cells. It has been suggested that let-7a-5p, Stat3, and hnRNP-A1 form a feedback loop to regulate PKM2 expression and modulate glucose metabolism in breast cancer cells, suggesting that inhibiting STAT3-related metabolism may inhibit breast cancer proliferation [42].…”

Section: The Role Of Stat3 In Breast Cancer Proliferation and Apoptosismentioning

confidence: 99%

Role of STAT3 signaling pathway in breast cancer

2020

View full text Add to dashboard Cite

Breast cancer has grown to be the second leading cause of cancer-related deaths in women. Only a few treatment options are available for breast cancer due to the widespread occurrence of chemoresistance, which emphasizes the need to discover and develop new methods to treat this disease. Signal transducer and activator of transcription 3 (STAT3) is an early tumor diagnostic marker and is known to promote breast cancer malignancy. Recent clinical and preclinical data indicate the involvement of overexpressed and constitutively activated STAT3 in the progression, proliferation, metastasis and chemoresistance of breast cancer. Moreover, new pathways comprised of upstream regulators and downstream targets of STAT3 have been discovered. In addition, small molecule inhibitors targeting STAT3 activation have been found to be efficient for therapeutic treatment of breast cancer. This systematic review discusses the advances in the discovery of the STAT3 pathways and drugs targeting STAT3 in breast cancer.

show abstract

PKM2 promotes glucose metabolism through a let‐7a‐5p/Stat3/hnRNP‐A1 regulatory feedback loop in breast cancer cells

Cited by 52 publications

References 40 publications

Polo-like kinase 3 inhibits glucose metabolism in colorectal cancer by targeting HSP90/STAT3/HK2 signaling

Polo-like kinase 3 inhibits glucose metabolism in colorectal cancer by targeting HSP90/STAT3/HK2 signaling

Role of miRNA in the regulation of cannabidiol-mediated apoptosis in neuroblastoma cells

Role of STAT3 signaling pathway in breast cancer

Contact Info

Product

Resources

About