Dataset Information

Loss of STAT5A promotes glucose metabolism and tumor growth through miRNA-23a-AKT signaling in hepatocellular carcinoma.

ABSTRACT: Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide. Here, we identified that increased miR-23a expression in HCC tissues was associated with worse survival. More importantly, we found that STAT5A was a target of miR-23a, whose levels significantly decreased in tumor tissues. Stable expression of STAT5A in Huh7 cells suppressed glucose metabolism and tumor growth. Finally, this study showed that increased miR-23a negatively regulated STAT5A, which further activated AKT signaling to enable rapid metabolism for accelerated tumor growth in HCC. Taken together, our results demonstrated that the miR-23a-STAT5A-AKT signaling pathway is critical to alter glucose metabolism in HCC and may offer new opportunities for effective therapy.

SUBMITTER: Jiang Y

PROVIDER: S-EPMC7858139 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature

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Loss of STAT5A promotes glucose metabolism and tumor growth through miRNA-23a-AKT signaling in hepatocellular carcinoma.

Jiang Yabo Y Tao Yongzhen Y Zhang Xiuping X Wei Xubiao X Li Min M He Xuxiao X Zhou Bin B Guo Weixing W Yin Huiyong H Cheng Shuqun S

Molecular oncology 20201122 2

Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide. Here, we identified that increased miR-23a expression in HCC tissues was associated with worse survival. More importantly, we found that STAT5A was a target of miR-23a, whose levels significantly decreased in tumor tissues. Stable expression of STAT5A in Huh7 cells suppressed glucose metabolism and tumor growth. Finally, this study showed that increased miR-23a negatively regulated STAT5A, which further activated AK ...[more]

PMID: 33155364

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Project description:Background and Aims: Cancer cells prefer aerobic glycolysis to maintain growth advantages, but the role of long non-coding RNAs (lncRNAs) in glycometabolism still remains unclear. Here we identified one cytoplasmic lncRNA LINC01554 as a significantly downregulated lncRNA in hepatocellular carcinoma (HCC) and aimed to investigate its role in cellular glucose metabolism in the development and progression of HCC. Methods: Quantitative real-time PCR was used to determine the expression level of LINC01554. Downregulation of LINC01554 by miR-365a at transcriptional level was assessed by luciferase reporter assay. Subcellular fractionation assay and RNA fluorescence in situ hybridization were performed to detect the subcellular localization of LINC01554. RNA pull-down assay, mass spectrometry, and RNA immunoprecipitation assay were used to identify the underlying molecular mechanisms. The tumor-suppressive function of LINC01554 was determined by both in vitro assay and nude mice xenograft model. Results: LINC01554 was frequently downregulated in HCC, which was significantly associated with tumor invasion (P = 0.005), tumor size (P = 0.041), tumor staging (P = 0.023) and shorter survival (P = 0.035) of HCC patients. Luciferase reporter assay unraveled that LINC01554 was negatively regulated by miR-365a. Subcellular fractionation assay and RNA FISH revealed the cytoplasmic predominance of LINC01554 in MIHA cells and HCC clinical samples. Ectopic expression of LINC01554 inhibited HCC cell growth, colony formation in soft agar, foci formation, and tumor formation in nude mice. LINC01554 promoted the ubiquitin-mediated degradation of PKM2 and inhibited Akt/mTOR signaling pathway to abolish aerobic glycolysis in HCC cells. Further study found that LINC01554-knockout could effectively reverse the tumor-suppressive effect of LINC01554. Conclusions: Our results identify LINC01554 as a novel tumor suppressor in HCC and unravel its underlying molecular mechanism in reprogramming cellular glucose metabolism. LINC01554 could possibly serve as a novel prognostic biomarker and provide the rationale for HCC therapy.

Dataset Information

Loss of STAT5A promotes glucose metabolism and tumor growth through miRNA-23a-AKT signaling in hepatocellular carcinoma.

Publications

Loss of STAT5A promotes glucose metabolism and tumor growth through miRNA-23a-AKT signaling in hepatocellular carcinoma.

Similar Datasets

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