LncRNA HOTAIR promotes the growth and metastasis of gastric cancer by sponging miR-1277-5p and upregulating COL5A1

Abstract

Background Emerging studies have shown that HOTAIR acts as an oncogene in gastric cancer (GC). However, its role in the extracellular matrix and in tumor immune infiltration remains unknown. Methods HOTAIR and COL5A1 levels were analyzed by bioinformatics analysis and validated by qRT-PCR, western blotting and immunohistochemistry assays. The regulatory relationships between components of the HOTAIR/miR-1277-5p/ COL5A1 axis and the role of this axis in GC were predicted by bioinformatics analysis, and validated by in vitro and in vivo experiments. The correlation between COL5A1 and GC immune infiltration was assessed by bioinformatics analysis and a COL5A1-based predictive nomogram was established using the Stomach Adenocarcinoma dataset from The Cancer Genome Atlas. Results We found that HOTAIR and COL5A1 were overexpressed in GC compared to normal controls, which predicted poor prognosis. The regulatory relationship of the HOTAIR/miR-1277-5p/COL5A1 axis in GC was demonstrated, and HOTAIR and COL5A1 were found to promote GC growth while miR-1277-5p exerted the reverse effects. In addition, COL5A1 was negatively associated with tumor purity but positively associated with immune infiltration, which suggested that COL5A1mediated GC growth may be partially mediated by the regulation of immune infiltration. Additionally, the established COL5A1-based nomogram showed that COL5A1 can serve as a prognostic biomarker in GC. Conclusions HOTAIR regulates GC growth by sponging miR-1277-5p and upregulating COL5A1, and COL5A1-mediated GC cell proliferation may be mediated by effects on the tumor microenvironment, which provides novel targets for GC treatment.

Identification of a Hypoxia-Related Signature for Predicting Prognosis and the Immune Microenvironment in Bladder Cancer

“…Accumulating researches indicated that COL5A1 might be a new prognostic candidate for many carcinomas (Chen et al, 2019;Cao et al, 2020). Besides, COL5A1 can accelerate the growth and progression of gastric cancer (Wei et al, 2020). HS3ST1 is a member of the heparan sulfate biosynthetic enzyme family and has been reported to be associated with the NF-kB signaling pathway in acute lymphocytic leukemia (Zhang et al, 2019).…”

Roles of the HOX Proteins in Cancer Invasion and Metastasis

“…Moreover, HOTAIR can act as a molecular sponge of miR-204, leading to an increase in HOXC8, promoting proliferation, migration and invasion in oesophageal cancer cells [128], whereas in cholangiocarcinoma, this process occurs through the modulation of miR-204-5p's interaction with HMGB1 [129]. Notwithstanding, HOTAIR promotes GC cell growth and metastasis by interfering in the miR-217/GPC5 [130], miR-1277-5p/COL5A1 [131], and miR-618/KLF12 axis, being that the last one induces metastasis by promoting the PI3K/ATK signalling pathway [132]. Recent findings have also related HOTAIR interference to Trastuzumab resistance in GC, through the sponging of miR-3030 and consequent upregulation of ERBB4 [133], which is responsible for activating the PI3K/ATK signalling pathway [134].…”

<p>Long Non-Coding RNA NCK1-AS1 Serves an Oncogenic Role in Gastric Cancer by Regulating miR-137/NUP43 Axis</p>

“…Li et al multiple lncRNAs were found to be abnormally expressed in GC through inhibiting or stimulating cellular malignant behaviors. [14][15][16] Dai et al reported lncRNA MALAT1 contributes the response of GC cells to cisplatin via regulating PI3K/AKT pathway. 14 Shi et al found that LINC00152 inhibits GC cell migration and invasion through alteration of the ERK/MAPK signaling pathway.…”

“…15 Wei et al revealed that increased expression of lncRNA HOTAIR stimulates GC growth by upregulating COL5A1 via sponging miR-1277-5p. 16 These studies uncovered the importance of lncRNAs in regulating GC progression. NCK1-AS1 was found to serve as oncogenic lncRNA in several cancers.…”