Long non‑coding RNA CASC15 facilitates esophageal squamous cell carcinoma tumorigenesis via decreasing SIM2 stability via FTO‑mediated demethylation

Abstract

Long non-coding RNAs (lncRNAs) are involved in the regulation of esophageal squamous cell carcinoma (ESCC) progression. However, the function and mechanism of lncRNA cancer susceptibility candidate 15 (CASC15) are poorly defined. In the present study, tumor and normal adjacent tissues were collected from 45 patients with ESCC. Expression levels of CASC15, fat mass and obesity-associated (FTO) protein and single-minded 2 (SIM2) were examined via reverse transcription-quantitative PCR and western blot assays. Cell proliferation and apoptosis were evaluated via MTT, flow cytometry and caspase-3 activity assays, respectively. Additionally, an ESCC mouse xenograft model was used to assess the function of CASC15 in vivo . The interaction between FTO and CASC15/SIM2 was analyzed via RNA immunoprecipitation and RNA pull-down assays. The results revealed that CASC15 expression was elevated in ESCC tissues, and patients with ESCC exhibiting high CASC15 expression had a poor prognosis. CASC15-knockdown inhibited ESCC cell proliferation and facilitated apoptosis. Additionally, CASC15-knockdown decreased the growth of ESCC xenograft tumors. CASC15 decreased SIM2 stability via FTO-mediated demethylation. Additionally, FTO loss markedly weakened CASC15-mediated pro-proliferative and anti-apoptotic effects in ESCC cells. SIM2 downregulation weakened the effect of CASC15-knockdown on cell proliferation and inhibited the increase of the apoptotic rate and caspase-3 activity induced by CASC15 depletion in ESCC cells. In conclusion, CASC15 promoted ESCC tumorigenesis by decreasing SIM2 stability via FTO-mediated demethylation.

Long non-coding RNA LINC00680 functions as a ceRNA to promote esophageal squamous cell carcinoma progression through the miR-423-5p/PAK6 axis

“…Accumulated researches have focused on the functions and mechanisms of lncRNAs to discover novel diagnostic markers and therapeutic targets for cancers [ 63 – 66 ]. In this study, a large number of lncRNAs were identified to be expressed aberrantly through transcriptomic analysis of ESCC tumor samples and matched normal tissues, of which LUCAT1 [ 45 ], CASC15 [ 47 ], MIAT [ 48 ], ZNF503-AS1, [ 67 ] and STXBP5-AS1 [ 68 ] have been shown to either promote or inhibit tumorigenesis in ESCC as well as other malignant tumors. In particular, the high expression of LINC00680, AC092910.3, MIR4435-2HG, and GSEC were found to be correlated with poor prognosis in ESCC patients.…”

Long Non-coding RNAs WithIn VitroandIn VivoEfficacy in Preclinical Models of Esophageal Squamous Cell Carcinoma Which Act by a Non-microRNA Sponging Mechanism

“…CASC15 targets single-minded 2. lncRNA cancer susceptibility candidate 15 (CASC15) (Figure 4 and Figure 6F) has been shown to be increased in ESSC tissues (130). CASC15 knockdown decreased proliferation and promoted apoptosis in Eca109 and KYSE450 ESCC cells in vitro.…”

LncRNAs and Chromatin Modifications Pattern m6A Methylation at the Untranslated Regions of mRNAs

“…In a similar study, the lncRNA GAS-AS1 was found to promote the ALKBH5-dependent demethylation of GAS mRNA and inhibit cervical cancer proliferation ( Wang et al, 2019 ; Chen et al, 2020 ). Additionally, the lincRNA CASC15 is thought to recruit the demethylase FTO to SIM2, decreasing SIM2 mRNA stability and promoting esophageal cancer progression ( Qin et al, 2020 ). Furthermore, specific lncRNAs such as CACNA1G-AS1 and ACAP2-IT1 have been predicted to regulate m 6 A readers and writers expression ( Zheng et al, 2021 ).…”