SIRT1 promotes GLUT1 expression and bladder cancer progression via regulation of glucose uptake

Jiang

et al. 2020

Stem Cell Res Ther

Background: The functions of HULC have been demonstrated in several cancers. However, its mechanism has not been elucidated in human liver cancer stem cells. Methods: Liver cancer stem cells were isolated from Huh7 cells; gene infection and tumorigenesis test in vitro and in vivo were performed. Results: We demonstrate that HULC promotes growth of liver cancer stem cells in vitro and in vivo. Mechanistically, HULC enhances the expression of Sirt1 dependent on miR675 and then induces the cellular autophagy through Sirt1. HULC enhances CyclinD1 and thereby increases pRB and inhibited P21 WAF1/CIP 1 via autophagy-miR675-PKM2 pathway in human liver cancer stem cells. Ultimately, our results demonstrate that CyclinD1 is required for the oncogenic functions of HULC in liver cancer stem cells. Conclusions: It reveals the key molecular signaling pathways for HULC and provides important basic information for finding effective tumor therapeutic targets based on HULC.

Section: Discussionsupporting

confidence: 93%

Long noncoding RNA HULC accelerates the growth of human liver cancer stem cells by upregulating CyclinD1 through miR675-PKM2 pathway via autophagy

Jiang

et al. 2020

Stem Cell Res Ther

“…SIRT1 has been reported to act as oncogene and promoted tumorigenesis in a class of cancers, including bladder cancer, angiosarcoma, gastric cancer and renal adenocarcinoma 32–35. In diabetic conditions, inhibition of SIRT1 induced early calcification and led to cellular senescence of vascular smooth muscle cells 36.…”

Section: Discussionmentioning

confidence: 99%

<p>MiR-29a function as tumor suppressor in cervical cancer by targeting SIRT1 and predict patient prognosis</p>

Peng

Niu

et al. 2019

OTT

IntroductionCervical cancer is the second most frequently malignant tumors in females and metastasis is a challenge of the treatment of cervical cancer. MiR-29a is usually low expressed in several tumors and its functions in cervical cancer remain unclear.Patients and methodsThe quantitative real-time polymerase chain reaction was employed to assess the expression of miR-29a and the Sirtuin-1 (SIRT1). Cell metastatic ability was assessed using Transwell and Western blot assays. The dual-luciferase reporter assay was performed to verify that miR-29a targeted to the 3’-untranslated region (UTR) of SIRT1 mRNA.ResultsMiR-29a was low expressed in cervical cancer and downregulation of miR-29a was associated with poor outcome. MiR-29a regulated the expression of SIRT1 by targeting to its 3’-UTR of mRNA in HeLa cells. SIRT1 was upregulated in cervical cancer tissues and cells in comparison with the non-tumor tissues and normal cells. Upregulation of SIRT1 predicted worse outcome of cervical cancer patients. MiR-29a was participated in the migration, invasion and epithelial–mesenchymal transition (EMT) in cervical cancer through directly targeting to the 3’-UTR of SIRT1 mRNA. SIRT1 reversed partial roles of miR-29a on metastasis in cervical cancer.ConclusionmiR-29a suppressed migration, invasion and EMT by directly targeting to SIRT1 in cervical cancer. The newly identified miR-29a/SIRT1 axis provides novel insight into the pathogenesis of cervical cancer.

“…TAZ and Hippo pathway are also participated in metabolism modulation, such as to regulate glycolysis, lipogenesis, and glutaminolysis [10][11][12][13] . Interestingly, a growing body of evidence has veri ed that glycometabolism might modulate cell growth, migration and progression in bladder cancer [55][56][57] . Actually, while normal cells acquire energy for physiological processes from the oxidation of pyruvate, cancer cells rely on aerobic glycolysis to generate energy and compound for their aberrant growth and metastasis.…”

Section: Discussionmentioning

confidence: 99%

A positive feedback loop between TAZ and miR-942-3p modulates proliferation, migration, epithelial-mesenchymal transition process and glycometabolism in human bladder cancer

Fan

Zhou

et al. 2020

Preprint

Background: Transcriptional co-activator with PDZ-binding motif (TAZ) has been reported to involve in tumor progression, epithelial-mesenchymal transition (EMT) process and glycometabolism modulation. Herein, the underlying molecular mechanisms of TAZ-induced biological effects in bladder cancer were discovered; Methods: qRT-PCR, western blot and immunohistochemistry were performed to determine the level of TAZ in bladder cancer cells and tissues; CCK-8 assay, Colony formation assay, wound healing assay and Transwell assay were performed to evaluate the functions of TAZ, miR-942-3p and GAS1. qRT-PCR and western blot were used to determine the expression levels of related genes. Chromatin immunoprecipitation and dual-luciferase reporter assay confirmed the interaction between TAZ and miR-942. In vivo tumorigenesis assay and colorimetric assay of glycolysis were also conducted; Results: We determined the upregulation and vital roles of TAZ in bladder cancer. TAZ-induced upregulation of miR-942-3p amplified upstream signaling by inhibiting the expression of large tumor suppressor 2 (LATS2, a TAZ inhibitor). MiR-942-3p attenuated the suppression of cell proliferation, EMT process and glycolysis induced by TAZ knockdown. Further, miR-942-3p resulted in restrained expression of growth arrest-specific 1 (GAS1) to modulate biological functions; Conclusion: Our study identified a novel positive feedback loop between TAZ and miR-942-3p that regulates biological functions in bladder cancer cells via GAS1 expression, and illustrated that TAZ and miR-942-3p might be potential therapeutic targets for bladder cancer treatment.