LIX1-like Protein Promotes Liver Cancer Progression MiR-21-3p-mediated Inhibition of Fructose-1,6-bisphosphatase

Overview

Journal Acta Pharm Sin B

Publisher Elsevier

Specialty Pharmacology

Date 2021 Jul 5

PMID 34221869

Citations 11

Authors

Jie Zou

Xiaoyun Zhu

Dejuan Xiang

Yanqiu Zhang

Jie Li

Zhigui Su

Lingyi Kong

Hao Zhang

Affiliations

Soon will be listed here.

Abstract

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 significantly attenuated liver cancer initiation in mice. Functional studies indicated that LIX1L overexpression elevated proliferation, migratory, invasive capacities of HCC cells , and promoted liver cancer growth and metastasis 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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