lncRNA BBOX1-AS1 silencing inhibits esophageal squamous cell cancer progression by promoting ferroptosis via miR-513a-3p/SLC7A11 axis.

Long noncoding RNA BBOX1 antisense 1 (BBOX1-AS1) has been demonstrated to play important roles in several tumors. However, the expression and function of BBOX1-AS1 in esophageal squamous cell cancer (ESCC) have not been defined. Here, BBOX1-AS1 expression in 78 collected ESCC tissues, paired adjacent normal tissues, and ESCC cell lines were analyzed using quantitative real-time polymerase chain reaction. The overall survival of the patients was also studied. Cell proliferation, invasion, and migration were verified by constructing in vitro models. Additionally, cell apoptosis was determined by flow cytometry, and ferroptosis was examined using Ptgs2 detection and lipid-reactive oxygen species assays. The relationship between BBOX1-AS1 and downstream molecules was evaluated using RNA immunoprecipitation, western blotting, and luciferase reporter assays. The function of BBOX1-AS1 was studied in vivo using a xenograft model and immunohistochemistry. BBOX1-AS1 expression was significantly higher in ESCC tissues, indicating poor prognosis. Inhibition of BBOX1-AS1 reduced cell proliferation, slowed cell invasion and migration, and promoted apoptosis and ferroptosis in vitro. miR-513a-3p was verified as a specific target of BBOX1-AS1 in ESCC, whereas knockdown of miR-513a-3p reversed the suppressive function of BBOX1-AS1 silencing in TE-1 cells. Moreover, solute carrier family 7 member 11 (SLC7A11) is regulated by miR-513a-3p, which is mediated by BBOX1-AS1 in ESCC cells. In conclusion, downregulation of BBOX1-AS1 inhibits cell proliferation, and metastasis accelerates cell apoptosis and ferroptosis in ESCC by upregulating miR-513a-3p to reduce SLC7A11 expression. These findings may provide novel insights into the diagnosis and treatment of ESCC.

Pan C ，Chen G ，Zhao X ，Xu X ，Liu J ... -  《-》

BBOX1-AS1 Activates Hedgehog Signaling Pathway to Facilitate the Proliferation and Stemness of Esophageal Squamous Cell Carcinoma Cells via miR-506-5p/EIF5A/PTCH1 Axis.

This study aimed to unveil the specific function of lncRNA BBOX1 antisense RNA 1 (BBOX1-AS1) in ESCC cells and the underlying regulatory mechanism. Esophageal squamous cell carcinoma (ESCC) is a deadly disease. Molecular mechanisms essential to ESCC development and progression require in-depth investigation. Long noncoding RNAs (lncRNAs) have been suggested as crucial effectors in modulating tumor growth. RT-qPCR and western blot examined the expression of genes and proteins of concern, respectively. Colony formation and EdU assays assessed the changes in cell proliferation. Sphere formation assay also detected the stemness of ESCC cells. Bioinformatics prediction, along with mechanistic assays (FISH, Subcellular fractionation, RNA pull-down, RIP, and luciferase reporter), was conducted to explore the gene interactions and regulatory relationship. BBOX1-AS1 was observed to be aberrantly up-regulated in ESCC tissues and cell lines. BBOX1-AS1 depletion exerted suppressive impacts on ESCC cell proliferation and stemness, while BBOX1-AS1 overexpression led to the opposite consequences. Moreover, BBOX1-AS1 was verified to activate Hedgehog signaling pathway via up-regulating PTCH1, and BBOX1-AS1 could sponge miR-506-5p to up-regulate EIF5A, thus stabilizing PTCH1 mRNA. Rescue experiments indicated that BBOX1-AS1 could affect ESCC cell proliferation and stemness via modulation on PTCH1. To conclude, BBOX1-AS1 activates Hedgehog signaling pathway to facilitate the proliferation and stemness of ESCC cells via miR-506-5p/EIF5A/PTCH1 axis.

Hu L ，Cao H ，Zheng L ，Li R ... -  《-》

Silencing lncRNA SLC16A1-AS1 Induced Ferroptosis in Renal Cell Carcinoma Through miR-143-3p/SLC7A11 Signaling.

Li YZ ，Zhu HC ，Du Y ，Zhao HC ，Wang L ... -  《-》

LncRNA BBOX1-AS1 Contributes to the Progression of Esophageal Carcinoma by Targeting the miR-361-3p/COL5A1 Axis.

Long noncoding RNAs (lncRNAs) are known to participate in the progression of several cancers, including esophageal carcinoma (EC), a common malignancy of the digestive system. Although the role of the lncRNA-miRNA-mRNA regulatory network is crucial for the growth and progression of EC, the regulation of lncRNA BBOX1-AS1 (BBOX1 antisense RNA1) remains unclear. We performed reverse transcription-quantitative PCR (RT-qPCR) and western blotting to evaluate miR-361-3p, collagen type V alpha 1 chain (COL5A1), and BBOX1-AS1 expression levels in EC cells and tissues. The colony formation assay (CFA) and Cell Counting Kit-8 (CCK-8) were employed to identify EC cell proliferation, while western blotting was used to examine EC cell apoptosis and Bax and Bcl-2 expression levels. The effect of BBOX1-AS1 on EC proliferation was determined using an in vivo carcinogenesis assay. Correlation between COL5A1, BBOX1-AS1, and miR-361-3p was examined using the luciferase reporter system and RNA immunoprecipitation assay (RIP). Herein, we observed that BBOX1-AS1 expression levels were upregulated in EC cells and tissues. BBOX1-AS1 knockdown inhibited EC cell proliferation and conferred a pro-apoptotic effect. These results indicated a positive interaction between BBOX1-AS1 and miR-361-3p in EC and a negative association with miR-361-3p. COL5A1 was recognized as a downstream miR-361-3p target and was inversely related to miR-361-3p in EC. Therefore, BBOX1-AS1 expression suppressed cell apoptosis and promoted cell proliferation via the downregulation of miR-361-3p and upregulation of COL5A1 expression. Overall, BBOX1-AS1 facilitates EC progression via the miR-361-3p or COL5A1 axis, indicating that BBOX1-AS1 might be a potential therapeutic target for EC therapy.

Lu YH ，He DS ，Li Y ，Wang H ，Ma RD ... -  《-》

LncRNA ZEB2-AS1 promotes the proliferation, migration and invasion of esophageal squamous cell carcinoma cell through miR-574-3p/HMGA2 axis.

Xu JH ，Chen RZ ，Liu LY ，Li XM ，Wu CP ，Zhou YT ，Yan JD ，Zhang ZY ... -  《-》