The IncRNA MACC1-AS1 promotes gastric cancer cell metabolic plasticity via AMPK/Lin28 mediated mRNA stability of MACC1

被引：206

作者：

Zhao, Yang ^{[1
]}

Liu, Yajing ^{[1
]}

Lin, Li ^{[1
]}

Huang, Qiong ^{[1
]}

He, Wanming ^{[1
]}

Zhang, Shuyi ^{[1
]}

Dong, Shumin ^{[1
]}

Wen, Zhaowei ^{[1
]}

Rao, Jinjun ^{[2
]}

Liao, Wangjun ^{[1
]}

Shi, Min ^{[1
]}

机构：

[1] Southern Med Univ, Nanfang Hosp, Dept Oncol, Guangzhou, Guangdong, Peoples R China

[2] Southern Med Univ, Key Lab New Drug Screening Guangdong Prov, Sch Pharmaceut Sci, Guangzhou, Guangdong, Peoples R China

来源：

MOLECULAR CANCER | 2018年 / 17卷

基金：

中国国家自然科学基金;

关键词：

MACC1-AS1; MACC1; Long non-coding RNA; Gastric cancer; Metabolic plasticity; mRNA stability; LONG NONCODING RNA; STRESS; METASTASIS; GROWTH; EXPRESSION; PATHWAY; TUMORS; PROGRESSION; REGULATOR; CARCINOMA;

D O I：

10.1186/s12943-018-0820-2

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Background: Metabolic plasticity has been increasingly thought to be a determinant of tumor growth and metastasis. MACC1, a transcriptional regulator of MET, was recognized as an oncogene in gastric cancer (GC); however, its transcriptional or post-translational regulation was not clear. We previously reported the metabolic role of MACC1 in glycolysis to promote GC progression. MACC1-AS1 is the antisense lncRNA of MACC1, yet its function was previously unknown. Methods: We profiled and analyzed the expression of MACC1-AS1 utilizing the TCGA database as well as in situ hybridization using 123 pairs of GC tissues and matched adjacent normal gastric mucosa tissues (ANTs). The biological role of MACC1-AS1 in cell growth and metastasis was determined by performing in vitro and in vivo functional experiments. Glycolysis and antioxidant capabilities were assayed to examine its metabolic function. Further, the specific regulatory effect of MACC1-AS1 on MACC1 was explored transcriptionally and posttranscriptionally. Results: MACC1-AS1 was shown to be expressed significantly higher in GC tissues than in ANTs, which predicted poor prognosis in GC patients. MACC1-AS1 promoted GC cell proliferation and inhibited cell apoptosis under metabolic stress. Mechanistically, MACC1-AS1 stabilized MACC1 mRNA and post-transcriptionally augmented MACC1 expression. Further, MACC1-AS1 was shown to mediate metabolic plasticity through MACC1 upregulation and subsequent enhanced glycolysis and anti-oxidative capabilities, and this was suggested to be coordinated by the AMPK/Lin28 pathway. Conclusions: Elevated expression of MACC1-AS1 in gastric cancer tissues is linked to poor prognosis and promotes malignant phenotype upon cancer cells. MACC1-AS1 is elevated under metabolic stress and facilitates metabolic plasticity by promoting MACC1 expression through mRNA stabilization. Our study implicates lncRNA MACC1-AS1 as a valuable biomarker for GC diagnosis and prognosis.

引用

页数：16

共 38 条

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