Long non-coding RNAs (lncRNAs) play a crucial role in tumor generation and progression. However, the exact functional significance and underlying molecular mechanism by which lncRNA CERS6-AS1 operates in the context of lung adenocarcinoma (LUAD) remain unknown. We aimed to evaluate the potential role of the CERS6-AS1/miR-424-5p/ANLN axis in the progression of LUAD through bioinformatics and cytobehavioral experiments, and to provide a new insight into the combined treatment of LUAD. Based on the TCGA database, the expression of CERS6-AS1 in pan-cancer was evaluated, and its prognostic performance in LUAD was evaluated by ROC curve, survival curve and COX analysis. In addition, quantification of CERS6-AS1 expression levels in LUAD patients and lung cancer cells using quantitative real-time polymerase chain reaction (RT-qPCR), and further validate the functional significance of CERS6-AS1 in promoting the proliferation, migration, and invasion abilities of lung cancer cells. The competitive endogenous RNA (ceRNA) network was constructed, and miR-424-5p inhibitors were applied to CERS6-AS1 knockdown cells. The potential downstream genes associated with the regulatory axis of CERS6-AS1/miR-424-5p were analyzed by PPI network and gene enrichment analysis (KEGG). Finally, we evaluated the prognostic value of high expression of ANLN in LUAD and its effects on immune cell infiltration, tumor mutation burden, chemotherapy response, and immunotherapy. CERS6-AS1 expression was significantly elevated in both LUAD patients and lung cancer cells. In the CERS6-AS1 knockdown assay, the proliferation, invasion, migration and epithelial-mesenchymal transformation (EMT) of cancer cells were significantly inhibited. Notably, there was a prominent upregulation of miR-424-5p expression in cells where CERS6-AS1 was knocked down. Co-transfection of siRNA and miR-424-5p inhibitors into lung cancer cells restored the restriction on lung cancer cells. Anillin (ANLN) has been identified as a potential target gene for miR-424-5p and as a prognostic and immune biomarker associated with immune cell infiltration and tumor mutational burden in LUAD. Additionally, ANLN impacts the efficacy of chemotherapy and immunotherapy in LUAD patients. This study reveals a novel regulatory mechanism in which CERS6-AS1 may contribute to the progression of LUAD by influencing the expression of ANLN as a competitive sponge for miR-424-5p.

OBJECTIVE: CERS6 antisense RNA 1 (CERS6-AS1), a long non-coding RNA (lncRNA), plays a role in the malignant progression of a variety of cancers. However, it is unclear whether it affects the malignant behavior of cervical cancer (CC) cells.
METHODS: CERS6-AS1 and miR-195-5p expression was estimated in CC via qRT-PCR. CCK-8, caspase-3 activity, scratch, and Transwell assays were performed to detect CC cell viability, caspase-3 activity, migration, and invasion in vitro. A tumor xenograft experiment was designed to study the growth of CC tumors in vivo. RIP and luciferase reporter experiments verified the relationship between CERS6-AS1 and miR-195-5p.
RESULTS: CERS6-AS1 overexpression and poor miR-195-5p levels were observed in CC. Inhibition of CERS6-AS1 impaired the viability, invasion, and migration of CC cells, promoted apoptosis, and suppressed tumor growth. In terms of the underlying mechanism, CERS6-AS1, as a competitive endogenous RNA (ceRNA), participated in the regulation of miR-195-5p levels in CC cells. Functionally, miR-195-5p interference attenuated the inhibitory effect of CERS6-AS1 on the malignant behaviors of CC cells.
CONCLUSIONS: CERS6-AS1 acts as an oncogene in CC, in vivo and in vitro, by negatively regulating miR-195-5p.

BACKGROUND: Colon cancer (CC) belongs to a common cancer of digestive system. Long non-coding RNAs (lncRNAs) are dysregulated in numerous cancers and affect their development. The function of lncRNA CERS6 antisense RNA 1 (CERS6-AS1) in CC remains unclear.
METHODS: CERS6-AS1 expression in colon adenocarcinoma tissues and CC cell lines was assessed by The Cancer Genome Atlas database and quantitative real-time polymerase chain reaction analysis. The function of CERS6-AS1 in CC was analysed by 5-ethynyl-2\'-deoxyuridine, colony formation, flow cytometry, terminal deoxynucleotidyl transferase dUTP nick end labelling, wound healing, Transwell and immunofluorescence assays. Mechanistic analyses including RNA pull down, RNA-binding protein immunoprecipitation and luciferase reporter assay revealed the interaction between RNAs.
RESULTS: CERS6-AS1 expression was aberrantly upregulated in colon adenocarcinoma tissues and CC cell lines. CERS6-AS1 knockdown inhibited CC cell malignant phenotypes and in vivo tumour growth. CERS6-AS1 served as the competing endogenous RNA of microRNA-16-5p in CC, and microRNA-16-5p inhibition partly rescued the effects of CERS6-AS1 depletion on CC development. Mitochondrial calcium uniporter was targeted by microRNA-16-5p. Mitochondrial calcium uniporter upregulation completely remedied the influence of CERS6-AS1 silencing in CC progression. Moreover, CERS6-AS1 enhanced the stability of mitochondrial calcium uniporter messenger RNA via recruiting RNA-binding protein embryonic lethal abnormal vision like 1.
CONCLUSIONS: CERS6-AS1 promotes the development of CC via upregulating mitochondrial calcium uniporter expression.

OBJECTIVE: The purpose of this study was to explore the function and mechanism of LncRNA CERS6-AS1 on papillary thyroid cancer.
METHODS: CERS6-AS1, miR-497-5p, and LASP1 expression in papillary thyroid cancer tissues and cells were detected by RT-PCR. The relationship between CERS6-AS1 expression and clinical characteristics was analyzed, and overall survival was evaluated via Kaplan-Meier analysis. Cell activity was tested by cell counting kit-8, cell reactive oxygen species was detected by DCFH-DA method, and cell iron ion was detected by iron analysis kit. The relationship among CERS6-AS1, miR-497-5p, and LASP1 was confirmed by luciferase reporter gene detection, RNA pull-down detection, and RIP detection. The expression of related proteins was assessed by western blot or immunohistochemistry.
RESULTS: High level of CERS6-AS1 and LASP1 was detected in papillary thyroid cancer tissues and cells and predicted poor prognosis. In contrast, miR-497-5p was decreased in papillary thyroid cancer tissues and cells, which was positively correlated with prognosis. Silencing CERS6-AS1 suppressed cell viability and increased ferroptosis in papillary thyroid cancer. LASP1 was modulated by CERS6-AS1 through sponging miR-497-5p. Up-regulation of LASP1 or silencing miR-497-5p could weaken the effect of CERS6-AS1 on papillary thyroid cancer cells. Silencing CERS6-AS1 restrained the growth of xenografted tumors.
CONCLUSIONS: Our findings demonstrated that down-regulation of CERS6-AS1 reduced cell viability and amplified cell ferroptosis by modulating the miR-497-5p/LASP1 axis in papillary thyroid cancer.

Pancreatic cancer (PC) is a lethal malignancy that threatens human health. Long noncoding RNAs (lncRNAs) act as important mediators in PC development. Our study aimed to investigate the function and mechanism of lncRNA ceramide synthase 6 antisense RNA 1 (CERS6-AS1) in PC. As shown by RT-qPCR, CERS6-AS1 was significantly upregulated in PC cells and tissues. Silencing CERS6-AS1 suppressed PC cell viability and proliferation while enhancing cell apoptosis according to colony formation assays, EdU assays, and flow cytometry analyses. Mechanistically, CERS6-AS1 interacted with miR-195-5p to elevate the expression level of the WD repeat domain phosphoinositide interacting 2 (WIPI2), which is a downstream target gene of miR-195-5p in PC. Moreover, miR-195-5p expression was negatively associated with CERS6-AS1 expression (or WIPI2 expression) in PC tissues. Rescue assays revealed that WIPI2 overexpression rescued the effects of CERS6-AS1 deficiency on cell viability, proliferation, and apoptosis. In summary, CERS6-AS1 facilitates PC cell proliferation while inhibiting PC cell apoptosis by upregulating WIPI2 via miR-195-5p. This study might provide promising insight into the role of CERS6-AS1 in PC development.

Accumulating evidence indicates that long noncoding RNAs (lncRNAs) act as tumor promoters or suppressors in various types of cancer. Previous investigations suggest that ceramide synthase 6 (CERS6) antisense RNA 1 (CERS6-AS1) acts as an oncogene in breast cancer; however, its role in colorectal cancer is unknown. This study aimed to explore the molecular mechanism of CERS6-AS1 in colorectal cancer. Gene expression in colorectal cancer was examined using reverse transcription-quantitative polymerase chain reaction and western blot analyses. The viability and proliferation of colorectal cancer cells were measured by Cell Counting Kit-8 assays and colony formation assays. The migratory and invasive capacities of the colorectal cancer cells were assessed by Transwell assay. Cell stemness was examined by sphere-formation assay. Mechanistically, RNA pull-down assays, RNA immunoprecipitation assays, and luciferase reporter assays were performed to explore the relationship among CERS6-AS1, miR-15b-5p and spectrin beta, non-erythrocytic 2 (SPTBN2). Moreover, a xenograft tumor model was established to investigate the role of CERS6-AS1 in vivo. We found that CERS6-AS1 and SPTBN2 were highly expressed in colorectal cancer tissues and cells. CERS6-AS1 depletion inhibited cell viability, proliferation, migration, and invasion; the epithelial-mesenchymal transition process and stemness. It suppressed xenograft tumor growth in colorectal cancer. Moreover, SPTBN2 levels were positively regulated by CERS6-AS1 and negatively regulated by miR-15b-5p in colorectal cancer cells. Rescue assays revealed that SPTBN2 reversed the inhibitory effect of CERS6-AS1 deficiency on the malignant behaviors of colorectal cancer cells. Overall, the lncRNA CERS6-AS1 facilitates malignant phenotypes of colorectal cancer cells by targeting miR-15b-5p to upregulate SPTBN2.

Breast cancer (BC) leads to the highest mortality in women worldwide, characterized by inevitable proliferation and metastasis of BC cells. Mounting evidence confirm that lncRNAs play a significant role in the tumorigenesis and development of BC. lncRNA CERS6-AS1 is a novel discovery, and its role and molecular mechanism in BC has not been studied. In this study, it was discovered that CERS6-AS1 was overexpressed in BC tissues and cells. CERS6-AS1 accelerated cell proliferation and suppressed cell apoptosis in BC. Moreover, molecular mechanism exploration uncovered that there was a positive association between CERS6 and CERS6-AS1 (or IGF2BP3) expression in BC. Furthermore, IGF2BP3 serves as a RNA-binding protein for CERS6-AS1 and CERS6-AS1 promoted CERS6 mRNA stability by binding to IGF2BP3. In the end, rescue experiments verified that overexpression of CERS6 rescues the inhibition of CERS6-AS1 deficiency on BC progression in vitro and vivo. Taken together, these evidences suggested that CERS6-AS1 promoted the progression of BC by binding to IGF2BP3 and thus enhancing the stability of CERS6 mRNA, providing a new underlying therapeutic target for BC to improve prognosis.