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LIX1-like protein promotes liver cancer progression via miR-21-3p-mediated inhibition of fructose-1,6-bisphosphatase

Limb and CNS expressed 1 like (LIX1L) is over-expressed in several types of tumors. However, the function of LIX1L in glucose metabolism and hepatocellular carcinoma (HCC) progression remains elusive. Here we report that LIX1L is over-expressed in human HCC tissues, which predicts unfavorable progno...

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Autores principales: Zou, Jie, Zhu, Xiaoyun, Xiang, Dejuan, Zhang, Yanqiu, Li, Jie, Su, Zhigui, Kong, Lingyi, Zhang, Hao
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8245913/
https://www.ncbi.nlm.nih.gov/pubmed/34221869
http://dx.doi.org/10.1016/j.apsb.2021.02.005
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author Zou, Jie
Zhu, Xiaoyun
Xiang, Dejuan
Zhang, Yanqiu
Li, Jie
Su, Zhigui
Kong, Lingyi
Zhang, Hao
author_facet Zou, Jie
Zhu, Xiaoyun
Xiang, Dejuan
Zhang, Yanqiu
Li, Jie
Su, Zhigui
Kong, Lingyi
Zhang, Hao
author_sort Zou, Jie
collection PubMed
description Limb and CNS expressed 1 like (LIX1L) is over-expressed in several types of tumors. However, the function of LIX1L in glucose metabolism and hepatocellular carcinoma (HCC) progression remains elusive. Here we report that LIX1L is over-expressed in human HCC tissues, which predicts unfavorable prognosis. LIX1L deficiency in vivo significantly attenuated liver cancer initiation in mice. Functional studies indicated that LIX1L overexpression elevated proliferation, migratory, invasive capacities of HCC cells in vitro, and promoted liver cancer growth and metastasis in vivo. LIX1L knockdown up-regulated fructose-1,6-bisphosphatase (FBP1) expression to reduce glucose consumption as well as lactate production. Mechanistically, LIX1L increased miR-21-3p expression, which targeted and suppressed FBP1, thereby promoting HCC growth and metastasis. MiR-21-3p inhibitor could abrogate LIX1L induced enhancement of cell migration, invasion, and glucose metabolism. Inhibition of miR-21-3p suppressed tumor growth in an orthotopic tumor model. Our results establish LIX1L as a critical driver of hepatocarcinogenesis and HCC progression, with implications for prognosis and treatment.
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spelling pubmed-82459132021-07-02 LIX1-like protein promotes liver cancer progression via miR-21-3p-mediated inhibition of fructose-1,6-bisphosphatase Zou, Jie Zhu, Xiaoyun Xiang, Dejuan Zhang, Yanqiu Li, Jie Su, Zhigui Kong, Lingyi Zhang, Hao Acta Pharm Sin B Original Article Limb and CNS expressed 1 like (LIX1L) is over-expressed in several types of tumors. However, the function of LIX1L in glucose metabolism and hepatocellular carcinoma (HCC) progression remains elusive. Here we report that LIX1L is over-expressed in human HCC tissues, which predicts unfavorable prognosis. LIX1L deficiency in vivo significantly attenuated liver cancer initiation in mice. Functional studies indicated that LIX1L overexpression elevated proliferation, migratory, invasive capacities of HCC cells in vitro, and promoted liver cancer growth and metastasis in vivo. LIX1L knockdown up-regulated fructose-1,6-bisphosphatase (FBP1) expression to reduce glucose consumption as well as lactate production. Mechanistically, LIX1L increased miR-21-3p expression, which targeted and suppressed FBP1, thereby promoting HCC growth and metastasis. MiR-21-3p inhibitor could abrogate LIX1L induced enhancement of cell migration, invasion, and glucose metabolism. Inhibition of miR-21-3p suppressed tumor growth in an orthotopic tumor model. Our results establish LIX1L as a critical driver of hepatocarcinogenesis and HCC progression, with implications for prognosis and treatment. Elsevier 2021-06 2021-02-10 /pmc/articles/PMC8245913/ /pubmed/34221869 http://dx.doi.org/10.1016/j.apsb.2021.02.005 Text en © 2021 Chinese Pharmaceutical Association and Institute of Materia Medica, Chinese Academy of Medical Sciences. Production and hosting by Elsevier B.V. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Original Article
Zou, Jie
Zhu, Xiaoyun
Xiang, Dejuan
Zhang, Yanqiu
Li, Jie
Su, Zhigui
Kong, Lingyi
Zhang, Hao
LIX1-like protein promotes liver cancer progression via miR-21-3p-mediated inhibition of fructose-1,6-bisphosphatase
title LIX1-like protein promotes liver cancer progression via miR-21-3p-mediated inhibition of fructose-1,6-bisphosphatase
title_full LIX1-like protein promotes liver cancer progression via miR-21-3p-mediated inhibition of fructose-1,6-bisphosphatase
title_fullStr LIX1-like protein promotes liver cancer progression via miR-21-3p-mediated inhibition of fructose-1,6-bisphosphatase
title_full_unstemmed LIX1-like protein promotes liver cancer progression via miR-21-3p-mediated inhibition of fructose-1,6-bisphosphatase
title_short LIX1-like protein promotes liver cancer progression via miR-21-3p-mediated inhibition of fructose-1,6-bisphosphatase
title_sort lix1-like protein promotes liver cancer progression via mir-21-3p-mediated inhibition of fructose-1,6-bisphosphatase
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8245913/
https://www.ncbi.nlm.nih.gov/pubmed/34221869
http://dx.doi.org/10.1016/j.apsb.2021.02.005
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