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

• 作者: Jie Zou Xiaoyun Zhu Dejuan Xiang Yanqiu Zhang Jie Li Zhigui Su Lingyi Kong Hao Zhang
• 来源期刊: 药学学报（英文版）
• 年，卷（期）: 2021,（6）
• 所属期刊栏目: Original articles
• 页码范围: 1578-1591
• 页数: 14页
• 语种: 英文

摘要

Limb and CNS expressed 1 like (LIX1L) is over-expressed in several types of tumors.How-ever,the function of LIX1L in glucose metabolism and hepatocellular carcinoma (HCC) progression re-mains 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 capac-ities 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 sup-pressed 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.