CERS6-AS1 promotes cell proliferation and represses cell apoptosis in pancreatic cancer via miR-195-5p/WIPI2 axis.

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.

Gao KF ，Zhao YF ，Liao WJ ，Xu GL ，Zhang JD ... -  《-》

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

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.

Zhao SY ，Wang Z ，Wu XB ，Zhang S ，Chen Q ，Wang DD ，Tan QF ... -  《-》

LncRNA CERS6-AS1, sponging miR-6838-5p, promotes proliferation and invasion in cervical carcinoma cells by upregulating FOXP2.

Cervical cancer (CC) is a common disease in women characterized by high recurrence rate. LncRNA ceramide synthase 6 antisense RNA 1 (CERS6-AS1) has been found to play a crucial role in the progression of breast cancer and pancreatic cancer. Nevertheless, the regulatory role of CERS6-AS1 in CC remains largely unclear. Here, we found that the expression of CERS6-AS1 was upregulated in CC tissues and cell lines compared with adjacent tissues and normal human cervical epithelial cells. CERS6-AS1 overexpression promoted proliferation and invasion, and inhibited apoptosis in CC cells, while silencing of CERS6-AS1 led to the opposite results. CERS6-AS1 was verified as a sponge of miR-6838-5p by RNA pull-down and luciferase reporter gene assays. Functional investigations revealed that CERS6-AS1 knockdown inhibited proliferation and invasion, and promoted apoptosis in CC cells, which was reversed by miR-6838-5p inhibitor. Furthermore, forkhead box P2 (FOXP2) was identified as a target for miR-6838-5p, and overexpression of miR-6838-5p decreased the expression level of FOXP2. Besides, CERS6-AS1 was able to sponge miR-6838-5p to accelerate CC cell proliferation and invasion and inhibited cell apoptosis through upregulating FOXP2 expression. In general, CERS6-AS1 was able to regulate CC cell proliferation, invasion and apoptosis by the miR-6838-5p/FOXP2 axis, which suggested that CERS6-AS1 may be a potential target for the treatment of CC.

Yan K ，Hu C ，Liu C ，Chu G ，Wang X ，Ma S ，Li L ... -  《-》

Long Noncoding RNA CERS6-AS1 Accelerates the Proliferation and Migration of Pancreatic Cancer Cells by Sequestering MicroRNA-15a-5p and MicroRNA-6838-5p and Modulating HMGA1.

As one of the most aggressive human tumors, pancreatic cancer (PC) is accompanied by poor treatment and prognosis. Although emerging evidence has highlighted the importance of long noncoding RNAs in multiple cancers, the specific regulatory roles mostly remain obscure. Our aim was to disclose the role of CERS6 antisense RNA 1 (CERS6-AS1) in PC. Quantitative real-time polymerase chain reaction analysis was used to examine the expression of CERS6-AS1 in PC cell lines. Western blot analysis was used to assess the protein levels of high-mobility group AT-hook 1 (HMGA1). Colony formation, 5-ethynyl-20-deoxyuridine, transwell, and wound healing assays were performed to detect the functions of CERS6-AS1 on PC development. In addition, RNA pull-down, RNA immunoprecipitation, and luciferase reporter assays were implemented to delve into the regulatory mechanism of CERS6-AS1 in PC. CERS6-AS1 was significantly upregulated in PC. CERS6-AS1 silence obviously inhibited cell proliferation and migration in PC. Furthermore, CERS6-AS1 sponged microRNA-15a-5p (miR-15a-5p) and microRNA-6838-5p (miR-6838-5p) to regulate HMGA1. Moreover, rescue assays verified that CERS6-AS1 was involved in cell proliferation and migration in PC via targeting miR-15a-5p/miR-6838-5p/HMGA1 axis. CERS6-AS1 enhanced HMGA1 expression to contribute to the progression of PC by sequestering miR-15a-5p and miR-6838-5p.

Shen R ，Wang X ，Wang S ，Zhu D ，Li M ... -  《-》

Long non-coding RNA CERS6-AS1 facilitates the oncogenicity of pancreatic ductal adenocarcinoma by regulating the microRNA-15a-5p/FGFR1 axis.

Yun Z ，Meng F ，Li S ，Zhang P ... -  《Aging-US》