Novel role of miR-133a-3p in repressing gastric cancer growth and metastasis via blocking autophagy-mediated glutaminolysis

Zhang, Xing; Li, Zheng; Xuan, Zhe; Xu, Penghui; Wang, Weizhi; Chen, Zheng; Wang, Sen; Sun, Guangli; Xu, Jianghao; Xu, Zekuan

doi:10.1186/s13046-018-0993-y

Cited by 90 publications

(67 citation statements)

References 58 publications

(49 reference statements)

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“…miR‐133a has been reported as a tumor‐associated miRNA and played an important role in cancers such as colorectal cancer, bladder cancer, and pancreatic cancer . Our results found that miR‐133a‐3p can affect proliferation in GC (Figure B,C), and further affect the expression of proliferation marker genes PCNA and MKI67 (Figure D‐F).…”

Section: Discussionmentioning

confidence: 55%

miR‐133a‐3p/FOXP3 axis regulates cell proliferation and autophagy in gastric cancer

Zhang

Liu

et al. 2020

J of Cellular Biochemistry

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Although many methods and new therapeutic drugs have been developed, the overall survival rate and long-term survival rate of patients with gastric cancer (GC) are still not satisfactory. In this study, we investigated the effects of microRNA miR-133a-3p and transcription factor FOXP3 on proliferation and autophagy of GC cells and their interactions. Our results showed that knockdown of FOXP3 increased the proliferation and autophagy of GC cells.The relationship between FOXP3 and autophagy has not been reported previously. In addition, FOXP3 could directly bind the promoter region of TP53 and inhibit its expression. miR-133a-3p increased the proliferation and autophagy via decreasing the protein level of FOXP3 by targeting its 3′-UTR. Our research provides new insights into the development of GC and provides new ideas and theoretical basis for the clinical treatment of GC and the development of new drug targets. K E Y W O R D S autophagy, FOXP3, gastric cancer, miR-133a-3p, proliferation

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Section: Discussionmentioning

confidence: 55%

miR‐133a‐3p/FOXP3 axis regulates cell proliferation and autophagy in gastric cancer

Zhang

Liu

et al. 2020

J of Cellular Biochemistry

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“…It is important to consider that, through the autophagy process, gastric cancer cells recycle glutamine for glutaminolysis to promote survival and metastasis. Therefore, it was confirmed that the malignant behavior of gastric cancer cells was suppressed by blocking glutaminolysis through the inhibition of autophagy by miR-133a-3p [117] ( Figure 2).…”

Section: Mir-133a-3pmentioning

confidence: 64%

“…Zhang et al (2018) [117] identified miR-133a-3p as a tumor suppressor in gastric cancer cells. According to an analysis performed using The Cancer Genome Atlas (TCGA) database, the downregulation of miR-133a-3p was observed in gastric cancer samples as well as in gastric cancer-derived cell lines.…”

Section: Mir-133a-3pmentioning

confidence: 99%

Non-Coding RNAs as Key Regulators of Glutaminolysis in Cancer

Ortiz-Pedraza

Muñoz-Bello

Olmedo-Nieva

et al. 2020

IJMS

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Cancer cells exhibit exacerbated metabolic activity to maintain their accelerated proliferation and microenvironmental adaptation in order to survive under nutrient-deficient conditions. Tumors display an increase in glycolysis, glutaminolysis and fatty acid biosynthesis, which provide their energy source. Glutamine is critical for fundamental cellular processes, where intermediate metabolites produced through glutaminolysis are necessary for the maintenance of mitochondrial metabolism. These include antioxidants to remove reactive oxygen species, and the generation of the nonessential amino acids, purines, pyrimidines and fatty acids required for cellular replication and the activation of cell signaling. Some cancer cells are highly dependent on glutamine consumption since its catabolism provides an anaplerotic pathway to feed the Krebs cycle. Intermediate members of the glutaminolysis pathway have been found to be deregulated in several types of cancers and have been proposed as therapeutic targets and prognostic biomarkers. This review summarizes the main players in the glutaminolysis pathway, how they have been found to be deregulated in cancer and their implications for cancer maintenance. Furthermore, non-coding RNAs are now recognized as new participants in the regulation of glutaminolysis; therefore, their involvement in glutamine metabolism in cancer is discussed in detail.Int. J. Mol. Sci. 2020, 21, 2872 2 of 26 an increased glucose consumption in relation to normal differentiated tissues. Now we know that glutamine metabolism is as important as glucose metabolism for the production of macromolecules in cancer [1].Glutamine is an abundant amino acid involved in energy production, homeostasis in pro/antioxidant species and the activation of signaling pathways in cancer. In addition to the antioxidant glutathione (GSH), nucleotides, lipids and amino acids are formed from glutamine metabolism. All of these are needed for many metabolic functions such as growth, proliferation, cell survival and defense against oxidative stress [2]. Glutamine contributes, with reduced nitrogen, to the de novo biosynthesis of diverse nitrogen-containing compounds, such as purine and pyrimidine nucleotides, glucosamine-6-phosphate and nonessential amino acids.As glutamine is the most abundant amino acid in the blood and muscle tissue, normal proliferating cells use glutamine metabolism as an energy source, mediated by its catabolic products, glutamate and α-ketoglutarate (α-kG), the latter being an intermediate of the tricarboxylic acid cycle (TCA) or Krebs cycle [3]. In 1950, Harry Eagle observed that HeLa tumor cells require an excess of glutamine, in relation to other amino acids in the culture medium, for optimal growth. Furthermore, it has been reported that tumors consume glutamine faster than the surrounding normal tissue [4]. Moreover, most cancer cells are dependent on glutamine being unable to survive under glutamine starvation, an effect that has been termed glutamine addiction [5]. Various types of cancers are high...

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“…MiR-31 promotes EMT in esophageal squamous cell carcinoma through stimulating LATS2 expression [29]. MiR-133a-3p impedes tumor growth and cell metastasis in gastric cancer [30]. MiR-133a-3p boosts prostate cancer progression through activating PI3K/ AKT pathway [31].…”

Section: Discussionmentioning

confidence: 99%

ZEB1-AS1/miR-133a-3p/LPAR3/EGFR axis promotes the progression of thyroid cancer by regulating PI3K/AKT/mTOR pathway

Wen

2020

Cancer Cell Int

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Background: Thyroid cancer (TC) is a member of common malignant tumors in endocrine system. To develop effective treatment, further comprehension of understanding molecular mechanism in TC is necessary. In this research, we attempted to search the underlying molecular mechanism in TC. Methods: ZEB1-AS1 expression was analyzed via qRT-PCR analysis. CCK-8, colony formation, flow cytometry and TUNEL assays were used to evaluate TC cell growth. The interaction between miR-133a-3p and LPAR3, EGFR and ZEB1-AS1 was testified through using RNA pull down and luciferase reporter assays. Results: LPAR3 and EGFR were expressed at high levels in TC tissues and cell lines. Besides, both LPAR3 and EGFR could promote TC cell growth. Later, miR-133a-3p was searched as an upstream gene of LPAR3 and EGFR, and LPAR3 could partially rescue the suppressive effect of miR-133a-3p overexpression on TC progression, whereas the co-transfection of LPAR3 and EGFR completely restored the inhibition. Next, ZEB1-AS1 was confirmed as a sponge of miR-133a-3p. ZEB1-AS1 has a negative correlation with miR-133a-3p and a positive association with LPAR3 and EGFR through ceRNA analysis. Importantly, ZEB1-AS1 boosted the proliferation and suppressed the apoptosis in TC cells. Through restoration assays, we discovered that ZEB1-AS1 regulated LPAR3 and EGFR expression to mediate TC cell proliferation and apoptosis by sponging miR-133a-3p. Further investigation also indicated the oncogenic role of ZEB1-AS1 by mediating PI3K/AKT/mTOR pathway. Conclusions: ZEB1-AS1 could be an underlying biomarker in TC.

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Novel role of miR-133a-3p in repressing gastric cancer growth and metastasis via blocking autophagy-mediated glutaminolysis

Cited by 90 publications

References 58 publications

miR‐133a‐3p/FOXP3 axis regulates cell proliferation and autophagy in gastric cancer

miR‐133a‐3p/FOXP3 axis regulates cell proliferation and autophagy in gastric cancer

Non-Coding RNAs as Key Regulators of Glutaminolysis in Cancer

ZEB1-AS1/miR-133a-3p/LPAR3/EGFR axis promotes the progression of thyroid cancer by regulating PI3K/AKT/mTOR pathway

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