Long non-coding RNA HOXC-AS1 exerts its oncogenic effects in esophageal squamous cell carcinoma by interaction with IGF2BP2 to stabilize SIRT1 expression.

Long non-coding RNA HOXC cluster antisense RNA 1 (HOXC-AS1) is a novel lncRNA whose cancer-promoting effect in gastric cancer and nasopharyngeal carcinoma has already been demonstrated. However, its functions in esophageal squamous cell carcinoma (ESCC) remains unknown. LncRNAs can interact with RNA-binding proteins (RBPs) and affect gene expression levels through post-transcriptional regulation. Insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2) is a widely studied RBP, and sirtuin 1 also known as SIRT1 has been reported to be involved in cancer progression. Establishment of in vivo models, HE and immunohistochemistry staining verified the oncogenic effect of HOXC-AS1. The interaction relationship between HOXC-AS1, IGF2BP2 and SIRT1 was verified by RNA pulldown and RNA immunoprecipitation (RIP) assay. Relative expression and stability changes of genes were detected by qPCR and actinomycin D experiments. Finally, the effect of HOXC-AS1-IGF2BP2-SIRT1 axis on ESCC was verified by rescue experiments. HOXC-AS1 is highly expressed in ESCC cells and plays oncogenic effects in vivo. qPCR showed the positive relationship between HOXC-AS1 and SIRT1 following HOXC-AS1 knockdown or overexpression. RNA-pulldown, mass spectrometry and RIP assay demonstrated that IGF2BP2 is an RBP downstream of HOXC-AS1. Then, RIP and qPCR showed that IGF2BP2 could bind to SIRT1 mRNA and knockdown IGF2BP2 resulted in decreased SIRT1 mRNA level. Finally, a series of rescue assay showed that the HOXC-AS1-IGF2BP2-SIRT1 axis can affect the function of ESCC. LncRNA HOXC-AS1 acts as an oncogenic role in ESCC, which impacts ESCC progression by interaction with IGF2BP2 to stabilize SIRT1 expression.

Yang Z ，Wan J ，Ma L ，Li Z ，Yang R ，Yang H ，Li J ，Zhou F ，Ming L ... -  《-》

LncRNA MNX1-AS1 promotes progression of esophageal squamous cell carcinoma by regulating miR-34a/SIRT1 axis.

Long non-coding RNAs (lncRNAs) are powerful factors influencing the tumorigenesis and metastasis of multiple carcinomas. LncRNA MNX1-AS1 plays critical roles in the progression of tumor formation according to recent research, while its roles in esophageal squamous cell carcinoma (ESCC) remains unknown. The expression levels of lncRNA MNX1-AS1 were examined in ESCC tissues by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR). The role of lncRNA MNX1-AS1 was performed by WST-1 proliferation assays, migration and invasion assays. Besides, the molecular mechanism of lncRNA MNX1-AS1 was verified by online bioinformatics, qRT-PCR and rescue assays. MNX1-AS1 was signifcantly upregulated in ESCC tissues. It was conformed that high MNX1-AS1 expression was associated with ESCC lymph node metastasis. Moreover, we found that knockdown of MNX1-AS1 apparently suppressed the cell proliferation, migration, and invasion capacity. Flow cytometry analysis showed MNX1-AS1 regulated ESCC cell cycle and apoptosis progression. Mechanism analysis revealed that miR-34a inhibitor could rescue the influence of inhibiting MNX1-AS1 on ESCC cells migration by serving as competing endogenous RNA (ceRNAs). Furthermore, we found that miR-34a specifically targeted SIRTI. Taken together, we demonstrated that lncRNA MNX1-AS1/miR-34a/SIRT1 regulatory axis could play an important role in ESCC progression, and MNX1-AS1 may act as a novel potential biomarker for esophageal squamous cell carcinoma.

Chu J ，Li H ，Xing Y ，Jia J ，Sheng J ，Yang L ，Sun K ，Qu Y ，Zhang Y ，Yin H ，Wan J ，He F ... -  《-》

LncRNA RPL34-AS1 suppresses the proliferation, migration and invasion of esophageal squamous cell carcinoma via targeting miR-575/ACAA2 axis.

Long noncoding RNAs (lncRNAs) are abnormally expressed in a broad type of cancers and play significant roles that regulate tumor development and metastasis. However, the pathological roles of lncRNAs in esophageal squamous cell carcinoma (ESCC) remain largely unknown. Here we aimed to investigate the role and regulatory mechanism of the novel lncRNA RPL34-AS1 in the development and progression of ESCC. The expression level of RPL34-AS1 in ESCC tissues and cell lines was determined by RT-qPCR. Functional experiments in vitro and in vivo were employed to explore the effects of RPL34-AS1 on tumor growth in ESCC cells. Mechanistically, fluorescence in situ hybridization (FISH), bioinformatics analyses, luciferase reporter assay, RNA immunoprecipitation (RIP) assay and western blot assays were used to detect the regulatory relationship between RPL34-AS1, miR-575 and ACAA2. RPL34-AS1 was significantly down-regulated in ESCC tissues and cells, which was negatively correlated with overall survival in ESCC patients. Functionally, upregulation of RPL34-AS1 dramatically suppressed ESCC cell proliferation, colony formation, invasion and migration in vitro, whereas knockdown of RPL34-AS1 elicited the opposite function. Consistently, overexpression of RPL34-AS1 inhibited tumor growth in vivo. Mechanistically, RPL34-AS1 acted as a competing endogenous RNA (ceRNA) of miR-575 to relieve the repressive effect of miR-575 on its target ACAA2, then suppressed the tumorigenesis of ESCC. Our results reveal a role for RPL34-AS1 in ESCC tumorigenesis and may provide a strategy for using RPL34-AS1 as a potential biomarker and an effect target for patients with ESCC.

Zhang H ，Pan E ，Zhang Y ，Zhao C ，Liu Q ，Pu Y ，Yin L ... -  《BMC CANCER》

The m6A reader IGF2BP2 promotes the progression of esophageal squamous cell carcinoma cells by increasing the stability of OCT4 mRNA.

Zhao R ，Li T ，Zhao X ，Yang Z ，Ma L ，Wang X ... -  《-》

Lipid metabolism-related lncRNA SLC25A21-AS1 promotes the progression of oesophageal squamous cell carcinoma by regulating the NPM1/c-Myc axis and SLC25A21 expression.

Obesity alters metabolic microenvironment and is thus associated with several tumours. The aim of the present study was to investigate the role, molecular mechanism of action, and potential clinical value of lipid metabolism-related long non-coding RNA (lncRNA) SLC25A21-AS1 in oesophageal squamous cell carcinoma (ESCC). A high-fat diets (HFDs)-induced obesity nude mouse model was established, and targeted metabolomics analysis was used to identify critical medium-long chain fatty acids influencing the growth of ESCC cells. Transcriptomic analysis of public dataset GSE53625 confirmed that lncRNA SLC25A21-AS1 was a lipid metabolism-related lncRNA. The biological function of lncRNA SLC25A21-AS1 in ESCC was investigated both in vivo and in vitro. Chromatin immunoprecipitation(ChIP)assay, RNA-pull down, mass spectrometry, co-IP, and RNA IP(RIP) were performed to explore the molecular mechanism. Finally, an ESCC cDNA microarray was used to determine the clinical prognostic value of SLC25A21-AS1 by RT-qPCR. Palmitic acid (PA) is an important fatty acid component of HFD and had an inhibitory effect on ESCC cell lines. LncRNA SLC25A21-AS1 expression was downregulated by PA and associated with the proliferation and migration of ESCC cells in vitro and in vivo. Mechanistically, SLC25A21-AS1 interacted with nucleophosmin-1 (NPM1) protein to promote the downstream gene transcription of the c-Myc in the nucleus. In the cytoplasm, SLC25A21-AS1 maintained the stability of SLC25A21 mRNA and reduced the intracellular NAD+ /NADH ratio by influencing tryptophan catabolism. Finally, we demonstrated that high expression of SLC25A21-AS1 promoted resistance to cisplatin-induced apoptosis and was correlated with poor tumour grade and overall survival. HFD/PA has an inhibitory effect on ESCC cells and SLC25A21-AS1 expression. SLC25A21-AS1 promotes the proliferation and migration of ESCC cells by regulating the NPM1/c-Myc axis and SLC25A21 expression. In addition, lncRNA SLC25A21-AS1 may serve as a favourable prognostic biomarker and a potential therapeutic target for ESCC.

Liu Y ，Li C ，Fang L ，Wang L ，Liu H ，Tian H ，Zheng Y ，Fan T ，He J ... -  《Clinical and Translational Medicine》