Blocking the IGF2BP1-promoted glucose metabolism of colon cancer cells via direct de-stabilizing mRNA of the LDHA enhances anticancer effects

Zhang, Xiangliang; Li, Kejun; Jiao, Feng; Liu, Gaojie; Feng, Yongzeng

doi:10.1016/j.omtn.2020.12.020

Cited by 26 publications

(25 citation statements)

References 27 publications

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“…In OS cells, IGF2BP1 was upregulated in tumor tissues and promoted the growth and metastasis of cancer cells [ 33 , 34 ]. Consistent with the results of the current study, IGF2BP1 could bind with LDHA 3′-UTR, thus resulting in enhanced LDHA mRNA stability and increased glycolysis in colon cancer cells [ 15 ]. Additionally, IGF2BP1 silencing could increase the effectiveness of hyperthermia therapy in colon cancer cells [ 15 ].…”

Section: Discussionsupporting

confidence: 91%

IGF2BP1-regulated expression of ERRα is involved in metabolic reprogramming of chemotherapy resistant osteosarcoma cells

Peng

He³

et al. 2022

J Transl Med

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Doxorubicin (Dox) is the standard treatment approach for osteosarcoma (OS), while acquired drug resistance seriously attenuates its treatment efficiency. The present study aimed to investigate the potential roles of metabolic reprogramming and the related regulatory mechanism in Dox-resistant OS cells. The results showed that the ATP levels, lactate generation, glucose consumption and oxygen consumption rate were significantly increased in Dox-resistant OS cells compared with parental cells. Furthermore, the results revealed that the increased expression of estrogen-related receptor alpha (ERRα) was involved in metabolic reprogramming in chemotherapy resistant OS cells, since targeted inhibition of ERRα restored the shifting of metabolic profiles. Mechanistic analysis indicated that the mRNA stability, rather than ERRα transcription was markedly increased in chemoresistant OS cells. Therefore, it was hypothesized that the 3ʹ-untranslated region of ERRα mRNA was methylated by N6-methyladenine, which could further recruit insulin-like growth factor 2 mRNA binding protein 1 (IGF2BP1) to suppress mRNA decay and increase mRNA stability. IGF2BP1 knockdown downregulated ERRα and reversed the metabolic alteration of resistant OS cells. Additionally, the oncogenic effect of the IGF2BP1/ERRα axis on Dox-resistant OS cells was verified by in vitro and in vivo experiments. Clinical analysis also revealed that the expression levels of IGF2BP1 and ERRα were associated with the clinical progression of OS. Collectively, the current study suggested that the IGF2BP1/ERRα axis could regulate metabolic reprogramming to contribute to the chemoresistance of OS cells.

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Section: Discussionsupporting

confidence: 91%

IGF2BP1-regulated expression of ERRα is involved in metabolic reprogramming of chemotherapy resistant osteosarcoma cells

Peng

He³

et al. 2022

J Transl Med

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“…Nonetheless, all three IGF2BPs are highly expressed and function as independent prognostic factors in a variety of cancers, including lung cancer 89 , 90 , liver cancer 91 - 93 , breast cancer 94 , 95 , colorectal cancer 96 - 98 , pancreatic cancer 99 - 101 , prostate cancer 102 , bladder cancer 103 - 105 , thyroid cancer 106 - 108 , gastric cancer 109 , 110 , renal cell carcinoma 111 , ovarian cancer 112 , 113 , esophageal squamous cell carcinoma 114 , 115 , acute myeloid leukemia 116 . In addition to the high expression of the IGF2BPs itself, intercellular communication factors, such as tumor-secreted extracellular vesicles (EVs), can maintain the stability of IGF2BPs in cells to promote the development of cancer.…”

Section: The Oncogenic Role Of Igf2bps In Cancermentioning

confidence: 99%

The role of Insulin-like growth factor 2 mRNA-binding proteins (IGF2BPs) as m⁶A readers in cancer

Sun¹,

Cao²,

Du³

et al. 2022

Int. J. Biol. Sci.

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RNA can be modified by over 170 types of distinct chemical modifications, and the most abundant internal modification of mRNA in eukaryotes is N6-methyladenosine (m 6 A). The m 6 A modification accelerates mRNA process, including mRNA splicing, translation, transcript stability, export and decay. m 6 A RNA modification is installed by methyltransferase-like proteins (writers), and potentially removed by demethylases (erasers), and this process is recognized by m 6 A-binding proteins (readers). Notably, alterations of m 6 A-modified proteins (writers, erasers and readers) are involved in the tumorigenesis, progression and metastasis. Importantly, the fate of m 6 A-methylated mRNA is mediated mostly through m 6 A readers, and among these readers, insulin-like growth factor 2 mRNA-binding proteins (IGF2BPs) are unique RNA-binding proteins (RBPs) that stabilize their targets mRNA via m 6 A modification. In this review, we update the writers, erasers and readers, and their cross-talks in m 6 A modification, and briefly discuss the oncogenic role of IGF2BPs in cancer. Most importantly, we mainly review the up-to-date knowledges of IGF2BPs (IGF2BP1/2/3) as m 6 A readers in an m 6 A-modified manner in cancer progression.

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“…The immediate target of IGF2BP-1 in this study was the LDHA mRNA. The authors conclude that targeting the IGF2BP-1-LDHA-glycolysis pathway may be a promising therapeutic approach to enhance the anticancer effects of HT treatment [ 241 ].…”

Section: Therapeutic Strategies For Reduction Of Metabolic Glucose Disorders In Crcmentioning

confidence: 99%

Insulin-Like Growth Factor 1 (IGF-1) Signaling in Glucose Metabolism in Colorectal Cancer

Kasprzak

2021

IJMS

103

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Colorectal cancer (CRC) is one of the most common aggressive carcinoma types worldwide, characterized by unfavorable curative effect and poor prognosis. Epidemiological data re-vealed that CRC risk is increased in patients with metabolic syndrome (MetS) and its serum components (e.g., hyperglycemia). High glycemic index diets, which chronically raise post-prandial blood glucose, may at least in part increase colon cancer risk via the insulin/insulin-like growth factor 1 (IGF-1) signaling pathway. However, the underlying mechanisms linking IGF-1 and MetS are still poorly understood. Hyperactivated glucose uptake and aerobic glycolysis (the Warburg effect) are considered as a one of six hallmarks of cancer, including CRC. However, the role of insulin/IGF-1 signaling during the acquisition of the Warburg metabolic phenotypes by CRC cells is still poorly understood. It most likely results from the interaction of multiple processes, directly or indirectly regulated by IGF-1, such as activation of PI3K/Akt/mTORC, and Raf/MAPK signaling pathways, activation of glucose transporters (e.g., GLUT1), activation of key glycolytic enzymes (e.g., LDHA, LDH5, HK II, and PFKFB3), aberrant expression of the oncogenes (e.g., MYC, and KRAS) and/or overexpression of signaling proteins (e.g., HIF-1, TGF-β1, PI3K, ERK, Akt, and mTOR). This review describes the role of IGF-1 in glucose metabolism in physiology and colorectal carcinogenesis, including the role of the insulin/IGF system in the Warburg effect. Furthermore, current therapeutic strategies aimed at repairing impaired glucose metabolism in CRC are indicated.

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Blocking the IGF2BP1-promoted glucose metabolism of colon cancer cells via direct de-stabilizing mRNA of the LDHA enhances anticancer effects

Cited by 26 publications

References 27 publications

IGF2BP1-regulated expression of ERRα is involved in metabolic reprogramming of chemotherapy resistant osteosarcoma cells

IGF2BP1-regulated expression of ERRα is involved in metabolic reprogramming of chemotherapy resistant osteosarcoma cells

The role of Insulin-like growth factor 2 mRNA-binding proteins (IGF2BPs) as m⁶A readers in cancer

Insulin-Like Growth Factor 1 (IGF-1) Signaling in Glucose Metabolism in Colorectal Cancer

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Blocking the IGF2BP1-promoted glucose metabolism of colon cancer cells via direct de-stabilizing mRNA of the LDHA enhances anticancer effects

Cited by 26 publications

References 27 publications

IGF2BP1-regulated expression of ERRα is involved in metabolic reprogramming of chemotherapy resistant osteosarcoma cells

IGF2BP1-regulated expression of ERRα is involved in metabolic reprogramming of chemotherapy resistant osteosarcoma cells

The role of Insulin-like growth factor 2 mRNA-binding proteins (IGF2BPs) as m6A readers in cancer

Insulin-Like Growth Factor 1 (IGF-1) Signaling in Glucose Metabolism in Colorectal Cancer

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The role of Insulin-like growth factor 2 mRNA-binding proteins (IGF2BPs) as m⁶A readers in cancer