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Written | Hu Xiaohua Enhanced glycolytic activity is a major metabolic feature of tumors, but its underlying molecular mechanism and its role in cancer progression have not been clearly studied
.
Among them, long-chain non-coding RNAs (lncRNAs) have been reported to regulate tumor sugar metabolism by controlling the expression of metabolic enzymes and transporters or acting on some signaling pathways, but the direct connection between lncRNA and tumor glycolysis has not yet been established.
Build
.
NEAT1 is a highly abundant lncRNA, which was first discovered to be a structural component of nuclear paraspeckles and is closely related to the occurrence of tumors [1]
.
There are two subtypes of NEAT1-NEAT1_1 (~3.
7kb) and NEAT1_2 (~23kb).
Among them, NEAT1_2 is essential for the formation of nuclear spots, while NEAT1_1 is mainly located outside of the nuclear spots and proved to be unnecessary for the formation of nuclear spots.
[2]
.
Therefore, the exact physiological function of NEAT1_1 in tumorigenesis is still unclear
.
On December 7, 2021, Min Sup Song and Je-Hyun Yoon from the University of Texas Anderson Center jointly published a research article titled NEAT1 is essential for metabolic changes that promote breast cancer growth and metastasis on Cell Metabolism.
It is revealed that lncRNA NEAT1 promotes the glycolysis of breast cancer cells by providing a scaffold for the PGK1/PGAM1/ENO1 glycolytic multienzyme complex, thereby promoting the proliferation and metastasis of breast cancer
.
In order to explore the role of NEAT1 in breast cancer progression, the authors knocked out NEAT1 in human luminal breast cancer model mice (MMTV-PyVT).
The results showed that the tumor growth, angiogenesis, lungs in Neat1-/- mice Metastasis and other indicators related to tumor malignancy are all reduced
.
On the contrary, overexpression of NEAT1 in tumor cells promotes tumor growth in mice
.
These results together indicate that NEAT1 can promote the occurrence and development of breast cancer
.
Considering that the occurrence of tumors is usually accompanied by an increase in glycolytic activity, the authors further investigated the relationship between NEAT1 and tumor glucose metabolism
.
Interestingly, the authors found that the levels of glycolytic terminal metabolites (including 3-PG, 2-PG, PEP, pyruvate and lactate) in Neat1-/- mouse tumors were reduced, while the levels of glycolytic upstream metabolites It is elevated
.
This indicates that NEAT1 may increase the metabolic flux at the end of glycolysis by metabolically reprogramming breast cancer
.
So how does NETA1 regulate glycolysis? Through mechanism research, the author found that NEAT1 will directly bind to several metabolic enzymes PGK1, PGAM1 and ENO1 (excluding PKM2) at the end of glycolysis, and NEAT1 will act as a scaffold to promote PGK1/PGAM1/ENO1 glycolytic multiple enzymes The formation of complexes increases the metabolic flow at the end of glycolysis
.
In addition, the authors also found that NEAT1 will respond to Glucose stimulation and enter the cytoplasm from the nucleus to the cytoplasm under the binding of Plnin to regulate the sugar metabolism of tumor cells
.
Finally, the authors proved that NEAT1_1 plays a unique and important role in the glycolysis, growth and invasion of breast cancer cells, while NEAT1_2, another subtype of NETA1, does not have this function.
.
In summary, the research team revealed that lncRNA NEAT1 is a new regulator of glycolysis pathway, and the high expression of NEAT1 promotes the occurrence, proliferation and metastasis of breast cancer
.
This discovery may provide a new treatment idea for advanced breast cancer
.
Original link: https://doi.
org/10.
1016/j.
cmet.
2021.
11.
011 Platemaker: 11 References 1.
Chakravarty, D.
, Sboner, A.
, Nair, SS, Giannopoulou, E.
, Li, R.
, Hennig, S.
, Mosquera, JM, Pauwels, J.
, Park, K.
, Kossai, M.
, et al.
(2014).
The oestrogen receptor alpha-regulated lncRNA NEAT1 is a critical modulator of prostate cancer.
Nat.
Commun.
5, 5383.
2.
Adriaens, C.
, Rambow, F.
, Bervoets, G.
, Silla, T.
, Mito, M.
, Chiba, T.
, Asahara, H.
, Hirose, T.
, Nakagawa, S.
, Jensen, TH, and Marine, JC (2019).
The long noncoding RNA NEAT1_1 is seemingly dispensable for normal tissue homeostasis and cancer cell growth.
RNA 25, 1681–1695 Reprint instructions [Original article] BioArt original article, individuals are welcome Reposting and sharing, reprinting without permission is prohibited, the copyright of all published works is owned by BioArt
.
BioArt reserves all statutory rights and offenders must be investigated
.
.
Among them, long-chain non-coding RNAs (lncRNAs) have been reported to regulate tumor sugar metabolism by controlling the expression of metabolic enzymes and transporters or acting on some signaling pathways, but the direct connection between lncRNA and tumor glycolysis has not yet been established.
Build
.
NEAT1 is a highly abundant lncRNA, which was first discovered to be a structural component of nuclear paraspeckles and is closely related to the occurrence of tumors [1]
.
There are two subtypes of NEAT1-NEAT1_1 (~3.
7kb) and NEAT1_2 (~23kb).
Among them, NEAT1_2 is essential for the formation of nuclear spots, while NEAT1_1 is mainly located outside of the nuclear spots and proved to be unnecessary for the formation of nuclear spots.
[2]
.
Therefore, the exact physiological function of NEAT1_1 in tumorigenesis is still unclear
.
On December 7, 2021, Min Sup Song and Je-Hyun Yoon from the University of Texas Anderson Center jointly published a research article titled NEAT1 is essential for metabolic changes that promote breast cancer growth and metastasis on Cell Metabolism.
It is revealed that lncRNA NEAT1 promotes the glycolysis of breast cancer cells by providing a scaffold for the PGK1/PGAM1/ENO1 glycolytic multienzyme complex, thereby promoting the proliferation and metastasis of breast cancer
.
In order to explore the role of NEAT1 in breast cancer progression, the authors knocked out NEAT1 in human luminal breast cancer model mice (MMTV-PyVT).
The results showed that the tumor growth, angiogenesis, lungs in Neat1-/- mice Metastasis and other indicators related to tumor malignancy are all reduced
.
On the contrary, overexpression of NEAT1 in tumor cells promotes tumor growth in mice
.
These results together indicate that NEAT1 can promote the occurrence and development of breast cancer
.
Considering that the occurrence of tumors is usually accompanied by an increase in glycolytic activity, the authors further investigated the relationship between NEAT1 and tumor glucose metabolism
.
Interestingly, the authors found that the levels of glycolytic terminal metabolites (including 3-PG, 2-PG, PEP, pyruvate and lactate) in Neat1-/- mouse tumors were reduced, while the levels of glycolytic upstream metabolites It is elevated
.
This indicates that NEAT1 may increase the metabolic flux at the end of glycolysis by metabolically reprogramming breast cancer
.
So how does NETA1 regulate glycolysis? Through mechanism research, the author found that NEAT1 will directly bind to several metabolic enzymes PGK1, PGAM1 and ENO1 (excluding PKM2) at the end of glycolysis, and NEAT1 will act as a scaffold to promote PGK1/PGAM1/ENO1 glycolytic multiple enzymes The formation of complexes increases the metabolic flow at the end of glycolysis
.
In addition, the authors also found that NEAT1 will respond to Glucose stimulation and enter the cytoplasm from the nucleus to the cytoplasm under the binding of Plnin to regulate the sugar metabolism of tumor cells
.
Finally, the authors proved that NEAT1_1 plays a unique and important role in the glycolysis, growth and invasion of breast cancer cells, while NEAT1_2, another subtype of NETA1, does not have this function.
.
In summary, the research team revealed that lncRNA NEAT1 is a new regulator of glycolysis pathway, and the high expression of NEAT1 promotes the occurrence, proliferation and metastasis of breast cancer
.
This discovery may provide a new treatment idea for advanced breast cancer
.
Original link: https://doi.
org/10.
1016/j.
cmet.
2021.
11.
011 Platemaker: 11 References 1.
Chakravarty, D.
, Sboner, A.
, Nair, SS, Giannopoulou, E.
, Li, R.
, Hennig, S.
, Mosquera, JM, Pauwels, J.
, Park, K.
, Kossai, M.
, et al.
(2014).
The oestrogen receptor alpha-regulated lncRNA NEAT1 is a critical modulator of prostate cancer.
Nat.
Commun.
5, 5383.
2.
Adriaens, C.
, Rambow, F.
, Bervoets, G.
, Silla, T.
, Mito, M.
, Chiba, T.
, Asahara, H.
, Hirose, T.
, Nakagawa, S.
, Jensen, TH, and Marine, JC (2019).
The long noncoding RNA NEAT1_1 is seemingly dispensable for normal tissue homeostasis and cancer cell growth.
RNA 25, 1681–1695 Reprint instructions [Original article] BioArt original article, individuals are welcome Reposting and sharing, reprinting without permission is prohibited, the copyright of all published works is owned by BioArt
.
BioArt reserves all statutory rights and offenders must be investigated
.
