Wang Q, etal., Cancer Genet. 2020 Jan;240:33-39. doi: 10.1016/j.cancergen.2019.11.001. Epub 2019 Nov 5.
Circular RNAs (circRNAs), resulting from the non-canonical splicing of linear pre-mRNAs, have permanently altered our perspectives toward cancer recently, especially in carcinogenesis and cancer progression. However, the roles of circRNAs in esophageal squamous cell carcinoma (ESCC) remain largely u
nknown. In the current study, circRNAs expression profiles are screened in ESCC, using plasma samples from 10 ESCC patients, including different TNM stages and 5 normal controls. Characteristics of circRNAs including length, types, and the possibility of binding to proteins are analyzed. Candidate tumor-related circRNAs are then quantitated in ESCC tissues, plasmas and cell lines. ESCC tissues can secret circRNAs into plasma and patients with high plasma circ-SLC7A5 are associated with high TNM stage, tending to have shorter overall survival than those with high levels. In addition, the biological characteristics of circ-SLC7A5 including location, miRNAs binding, m6A modification were analyzed. Our study reveals a novel prognosis biomarker of circ-SLC7A5, providing a preliminary landscape of circRNA expression for detection of ESCC.
Le Vee M, etal., Toxicol Appl Pharmacol. 2016 Jan 1;290:74-85. doi: 10.1016/j.taap.2015.11.014. Epub 2015 Nov 24.
The heterodimeric L-type amino acid transporter (LAT) 1/CD98hc is overexpressed in lung cancers with a poor prognosis factor. Factors that contribute to LAT1/CD98hc overexpression in lung cells remain however to be determined, but the implication of atmospheric pollution can be suspected. The presen
t study was therefore designed to analyze the effects of diesel exhaust particle (DEP) extract (DEPe) on LAT1/CD98hc expression in bronchial epithelial BEAS-2B cells. Exposure to DEPe up-regulated LAT1 and CD98hc mRNA levels in a concentration-dependent manner, with DEPe EC50 values (around 0.2 mug/mL) relevant to environmental situations. DEPe concomitantly induced LAT1/CD98hc protein expression and LAT1-mediated leucine accumulation in BEAS-2B cells. Inhibition of the aryl hydrocarbon receptor (AhR) pathway through the use of a chemical AhR antagonist or the siRNA-mediated silencing of AhR expression was next found to prevent DEPe-mediated induction of LAT1/CD98hc, indicating that this regulation depends on AhR, known to be activated by major chemical DEP components like polycyclic aromatic hydrocarbons. DEPe exposure was finally shown to induce mRNA expression and activity of matrix metalloproteinase (MMP)-2 in BEAS-2B cells, in a CD98hc/focal adhesion kinase (FAK)/extracellular regulated kinase (ERK) manner, thus suggesting that DEPe-mediated induction of CD98hc triggers activation of the integrin/FAK/ERK signaling pathway known to be involved in MMP-2 regulation. Taken together, these data demonstrate that exposure to DEPe induces functional overexpression of the amino acid transporter LAT1/CD98hc in lung cells. Such a regulation may participate to pulmonary carcinogenic effects of DEPs, owing to the well-documented contribution of LAT1 and CD98hc to cancer development.
Ding K, etal., J Biol Chem. 2018 Mar 16;293(11):3949-3964. doi: 10.1074/jbc.RA117.001103. Epub 2018 Jan 24.
Gastric cancer remains a malignancy with poor survival outcome. We herein report that GSE1, a proline-rich protein, possesses a role in the progression of human gastric cancer. The expression of GSE1 was observed to be much higher in human gastric cancer tissues compared with normal gastric tissues,
and GSE1 expression correlated positively with lymph node metastasis, histological grade, depth of invasion, and clinical stage in gastric cancer patients. Moreover, GSE1 expression was also associated with decreased post-operative relapse-free survival and overall survival in the cohort. The forced expression of GSE1 in gastric cancer cell lines resulted in increased cell proliferation, increased colony formation, enhanced cell migration, and invasion. Furthermore, forced expression of GSE1 also increased tumor size and enhanced lung metastasis in xenograft models. The depletion of endogenous GSE1 with shRNAs decreased the oncogenicity and invasiveness of gastric cancer cells both in vitro and in vivo In addition, GSE1 was determined to be a direct target of miR-200b and miR-200c. Furthermore, GSE1 positively regulated the downstream gene SLC7A5 (also known as LAT-1), which was scanned and verified from mRNA sequencing. GSE1 therefore possesses an oncogenic role in human gastric cancer, and targeted therapeutic approaches to inhibit GSE1 function in gastric cancer warrant further consideration.
