CERS6‐AS1 contributes to the malignant phenotypes of colorectal cancer cells by interacting with miR‐15b‐5p to regulate SPTBN2

Abstract

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, nonerythrocytic 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.

Linc00662 sponges miR-15b-5p to promote hypopharyngeal squamous cell carcinoma progression by facilitating cancer stem cell-like phenotypes

“…CSCs in oral/oropharyngeal squamous cell carcinoma enhance the tumorigenicity and self-renewal abilities of cancer cells in vivo 56 , 57 . Moreover, many studies have reported that Linc00662 enhances cell stemness in breast cancer/osteosarcoma by sponging miR-144-3p/miR-16-5p 22 , 35 , and that lncRNA CERS6-AS1 acts as an oncogene that facilitates xenograft tumor growth by binding to miR-15b-5p 29 . Consistent with previous findings, we demonstrate that the Linc00662 / miR-15b-5p axis affects tumor cell growth stemness.…”

“…In particular, lncRNAs act as sponges for miRNAs to influence the progression of cancer cell stemness [23][24][25][26][27]. There is increasing research on the roles of lncRNAs and miR-15b-5p in the occurrence and development of cancer [28][29][30]. However, the role and function of Linc00662 and miR-15b-5p in HSCC and their effects on tumor cell stemness have not been completely elucidated.…”

SPTBN2 regulates endometroid ovarian cancer cell proliferation, invasion and migration via ITGB4‑mediated focal adhesion and ECM receptor signalling pathway

“…In addition, Wang et al ( 12 ) suggested that SPTBN2 inhibition is implicated in halting proliferation, migration and invasion of endometrioid endometrial cancer cells. SPTBN2 upregulation promotes the proliferation, migration and invasion of colorectal cancer cells ( 30 ). Consistent with these findings, the present study demonstrated that SPTBN2 knockdown suppressed the proliferation, migration and invasion of A2780 cells, suggesting the oncogenic role of SPTBN2 in ovarian cancer.…”

Identification of a novel m6A-related lncRNAs signature and immunotherapeutic drug sensitivity in pancreatic adenocarcinoma

“…Another study demonstrated that the upregulated lncRNA JPX promoted lung cancer proliferation and metastasis by the JPX/miR-33a-5p/Twist1 axis activating Wnt/β-catenin signaling both in vitro and in vivo [ 7 ]. Zhao et al reported that the lncRNA CERS6-AS1 facilitates proliferation, migration and invasion in colorectal cancer cells by affecting miR-15b-5p to upregulate SPTBN [ 8 ].…”