lncRNA HOXC‐AS1 promotes gastric cancer via binding eIF4AIII by activating Wnt/β‐catenin signaling

Abstract

Background Long non‐coding RNAs (lncRNAs) function as oncogenes or tumor suppressor genes in several cancers. The present study aimed to determine the functions of lncRNA HOXC‐AS1 in gastric cancer (GC) in vitro. Methods A quantitative reverse transcriptase‐polymerase chain reaction (qRT‐PCR) was used to measure the expression of lncRNA HOXC‐AS1 in GC cell lines and normal cells. After silencing HOXC‐AS1 in GC cells, a cell counting kit‐8 assay monitored the viability of the cells. qRT‐PCR and western blot documented the EMT key genes in response to HOXC‐AS1 change. qRT‐PCR detected mRNA expression for eIF4AIII in GC and normal cell lines and cell viability was measured after an increase and decrease of eIF4AIII. RNA pull‐down and qRT‐PCR confirmed the binding in between. Apoptosis was compared by flow cytometry. The interplay between the two genes was surveyed by introduction of the sh‐HOXC‐AS1 and sh‐eIF4AIII and by assessing cell viability, EMT and Wnt/β‐catenin signaling. Results lncRNA HOXC‐AS1 expression is up‐regulated in GC cells and a decrease of lncRNA HOXC‐AS1 inhibited cell viability. Binding was validated by RNA pull‐down. Additionally, inhibition of eIF4AIII induced an increase of lncRNA HOXC‐AS1, thus promoting cell proliferation and the EMT process but deterring apoptosis of gastric cancer cells. Wnt/β‐catenin signaling was impeded by HOXC‐AS1 inhibition but restored by suppression of eIF4AIII. Conclusions HOXC‐AS1 may promote the proliferation and the EMT process and inhibit apoptosis by binding eIF4AIII via Wnt/β‐catenin signaling, which indicates that HOXC‐AS1/eIF4AIII might be an axis that could be further used as a biomarker to help with the diagnosis of GC.

Expression and Functional Roles of Eukaryotic Initiation Factor 4A Family Proteins in Human Cancers

“…Zhou et al reported that the long noncoding RNA (lncRNA), HOXC-AS1, inhibits GC cell apoptosis by binding eIF4A3 in the Wnt/β-catenin signaling pathway (Zhou et al, 2020). Another study has revealed that eIF4A3 may bind the circular RNA, PVRL3 (Sun et al, 2018).…”

“…In hepatocellular carcinoma, loss-of-function assays have shown that the silencing of eIF4A3 inhibits cell proliferation, migration, and EMT (Zhang et al, 2020). In GC tissues, eIF4A3 is downregulated compared to adjacent normal tissues, and the silencing of eIF4A3 increases lncRNA HOXC-AS1 expression, which promotes GC cell proliferation and EMT but represses apoptosis (Zhou et al, 2020). In cervical cancer, Sui et al reported that hsa_circ_0101119 promotes cell proliferation, migration, and invasion but suppresses apoptosis in cervical cancer via an interaction with eIF4A3 to inhibit TCEAL6 expression (Sui et al, 2021).…”

A Novel Immune-Related lncRNA Signature predict the Immune Landscape and Prognosis for Head and Neck Squamous Cell Carcinoma

“…In this study, some of the irlncRNAs in the process of modeling that have been already identi ed play an important role in malignant phenotypes of various cancer types, such as LINC01063 [24,25], HOXC-AS1 [26,27], LINC02454 [28,29] and SCAT1 [30]. Furthermore, previous reports have shown that LINC00460 [31], C5orf66-AS1 [32] and TMPO-AS1 [33] are associated with prognosis and treatment outcomes in HNSCC.…”

LncRNA NUTM2A‐AS1 positively modulates TET1 and HIF‐1A to enhance gastric cancer tumorigenesis and drug resistance by sponging miR‐376a

“…So far, a number of evidence show that lncRNAs are involved in tumor progression and cisplatin resistance of gastric cancer via various mechanisms. [25][26][27][28] NUTM2A-AS1 has not been studied in cancer, including gastric cancer. Our group, for the first time, prove that NUTM2A-AS1 accelerates tumor invasion, angiogenesis, and cisplatin resistance at cellular and animal level.…”

“…So far, a number of evidence show that lncRNAs are involved in tumor progression and cisplatin resistance of gastric cancer via various mechanisms 25‐28 . NUTM2A‐AS1 has not been studied in cancer, including gastric cancer.…”