Downregulation of long noncoding RNA LINC00460 expression suppresses tumor growth in vitro and in vivo in gastric cancer.

Abstract

BACKGROUND:

Long noncoding RNA have been indicated to be involved in tumor development. However, the role of LINC00460 in gastric cancer (GC) still remains large unknown. The current study is designed aiming at determining the effects of LINC00460 on GC progression.

PATIENTS AND METHODS:

The expression of LINC00460 in GC tissues and cells were detected by quantitative Real-Time Polymerase Chain Reaction (qRT-PCR). The cell proliferation, cell cycle distribution and cell invasion were evaluated by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide), flow cytometry analysis and transwell cell invasion assays. Western blot analysis was used to detect the WNT signaling related protein expression. Tumor xenograft assay was used to detect the effects of LINC00460 in vivo.

RESULTS:

In the study, we demonstrated that LINC00460 expression was higher in gastric cancer tissues compared to adjacent normal tissues. Higher LINC00460 expression associated with lymph node metastasis and advanced TNM stage. Furthermore, we showed that higher LINC00460 expression predicted a poor disease-free survival (DFS) and overall survival (OS) time of gastric cancer. Multivariate analysis showed that LINC00460 expression was an independent risk factor of GC prognosis. Furthermore, in vitro, we demonstrated that inhibition of LINC00460 expression suppressed cell proliferation, S phase cell number and cell invasion of gastric cancer cells compared to the control groups. In addition, we showed that downregulation of LINC00460 inhibited the Wnt/β-catenin signaling by downregulating c-Myc and β-catenin expression, which indicated LINC00460 could promote cell proliferation and invasion by activating Wnt/β-catenin signaling. In vivo, we also demonstrated that LINC00460 knockdown significantly suppressed cell proliferation.

CONCLUSIONS:

LINC00460 is a new type of molecule involved in the development of GC, which may become a potential target for the treatment of GC.

• Authors: Shuhua Zhang, Jianqun Xu, Hongjuan Wang, Hongrong Guo
• Journal: Cancer biomarkers : section A of Disease markers (Cancer Biomark) Vol. 24 Issue 4 Pg. 429-437 ( 2019) ISSN: 1875-8592 [Electronic] Netherlands
• PMID: 30909185 (Publication Type: Journal Article)

Chemical References

• Biomarkers, Tumor
• RNA, Long Noncoding

Topics

• Adult
• Aged
• Animals
• Biomarkers, Tumor
• Cell Line, Tumor
• Disease Models, Animal
• Female
• Gene Expression Regulation, Neoplastic
• Heterografts
• Humans
• Male
• Mice
• Middle Aged
• Neoplasm Metastasis
• Neoplasm Staging
• Prognosis
• RNA Interference
• RNA, Long Noncoding (genetics)
• Stomach Neoplasms (genetics, metabolism, mortality, pathology)
• Tumor Burden
• Wnt Signaling Pathway