LMX1A inhibits C-Myc expression through ANGPTL4 to exert tumor suppressive role in gastric cancer


Autoři: Peiyu Qian aff001;  Jian Li aff002;  Xiaohong Zhang aff002;  Fan Li aff002;  Songhua Bei aff002;  Huanqing Li aff002;  Qi Sun aff002;  Li Feng aff002
Působiště autorů: Minhang Fudan Medical Research Cooperative Development Research Institute, Minhang Hospital, Fudan University, Shanghai, Minhang District, Shanghai, P.R. China aff001;  Endoscopy Center, Minhang Hospital, Fudan University, Shanghai, Minhang District, Shanghai, P.R. China aff002
Vyšlo v časopise: PLoS ONE 14(9)
Kategorie: Research Article
doi: 10.1371/journal.pone.0221640

Souhrn

Our research group has showed that the LIM homeobox transcription factor 1 alpha (LMX1A) is inactivated in gastric cancers. Overexpression of LMX1A inhibits tumor growth. However, the mechanisms remains unclear. Considering LMX1A as a transcription factor, a comparison of RNA-seq between gastric cancer cells (GCCs) and GCCs with LMX1A overexpressed was performed to identify genes transcriptionally activated by LMX1A. Among the potential LMX1A target genes, angiopoietin-like 4 (ANGPTL4) has been reported to be an important tumor suppressor and thus was selected for further validation and research. Both LMX1A and ANGPTL4 showed downregulated expression in gastric cancer samples. More importantly, the expression of LMX1A is positively correlated with ANGPTL4, without including other family members in gastric cancer cell lines. What’s more, knockdown of ANGPTL4 rescued the tumor suppressive phenotype of LMX1A overexpression, which indicated that LMX1A upregulates ANGPTL4 to exert its role. Mechanistically, we found that LMX1A inhibited the expression of the oncogene C-Myc, which is alleviated by ANGPTL4 knockdown. In general, our results showed that LMX1A exerts its tumor suppressive role by activating ANGPTL4 to inhibit C-Myc.

Klíčová slova:

Gastric cancer – Gene regulation – Hyperexpression techniques – RNA extraction – RNA sequencing – Transcription factors – Tumor suppressor genes – Suppressor genes


Zdroje

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PLOS One


2019 Číslo 9

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