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. 2022 Jan-Dec:36:3946320221108271.
doi: 10.1177/03946320221108271.

LINC01088 regulates the miR-95/LATS2 pathway through the ceRNA mechanism to inhibit the growth, invasion and migration of gastric cancer cells

Zhuan Wen  1 , Yong Li  2 , Bibo Tan  2 , Zihao Chen  2 , Qun Zhao  2 , Ming Tan  2 , Yijie Zhao  2 , Yuxiang Xia  2 , Liqiao FanΔ  2
Affiliations

LINC01088 regulates the miR-95/LATS2 pathway through the ceRNA mechanism to inhibit the growth, invasion and migration of gastric cancer cells

Zhuan Wen et al. Int J Immunopathol Pharmacol. 2022 Jan-Dec.

Abstract

Background: In gastric cancer, a malignant condition with a dismal prognosis, long non-coding RNAs (LncRNAs) play a significant regulatory role. They often compete with microRNAs through the ceRNA mechanism to affect the expression of target mRNA. However, the specific clinical value and mechanism of action of LncRNA in gastric cancer are still unclear. Methods: This study detected the expression and clinical value of LINC01088 in gastric cancer tissues. Furthermore, the biological functions of LINC01088 and the regulation mechanism of the miR-95/LATS2 pathway were explored.Results: LINC01088 and LATS2 mRNA expression decreased, and miR-95 increased in gastric cancer tissues. LINC01088 has an excellent positive correlation with LATS2 mRNA, which may be a ceRNA pair; LINC01088 has binding sites with miR-95. Gene interference tests on gastric cancer cell lines revealed that LINC01088 could prevent gastric cancer cells from proliferating, invading, and migrating. The function of LINC01088 is achieved by regulating the miR-95/LATS2 pathway through the ceRNA mechanism.Conclusion: The results of this study show that LINC01088 expression is significantly reduced in gastric cancer tissues and cell lines. LINC01088 inhibits gastric cancer cells' proliferation, invasion, and migration by regulating the miR-95/LATS2 pathway via the ceRNA mechanism.

Keywords: LINC01088; gastric cancer; invasion; large tumor suppressor kinase 2; microRNA-95; migration; proliferation.

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Conflict of interest statement

Declaration of conflicting interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Figures

Figure 1.
Figure 1.
The expression of LINC01088 and miR-95 in gastric cancer tissues and the results of bioinformatics analysis. A The results of qRT-PCR showed that the expression level of LINC01088 in human gastric cancer tissue was significantly lower than that in adjacent tissues (p < .01). B The expression level of miR-95 in human gastric cancer tissues was significantly higher than that in adjacent tissues (p < .01). C The results of functional analysis of LINC01088 show that LINC01088 may directly regulate the expression of miR-95. D Bioinformatics results showed that the expression level of LINC01088 in human gastric cancer tissues was significantly lower than that in paracancerous tissues. E Correlation analysis showed that LINC01088 and LATS2 were co-existing in gastric cancer. The expression is presumed to be ceRNA.
Figure 2.
Figure 2.
Expression of LINC01088 and miR-95 in cell lines. A The qRT-PCR results showed that the expression of LINC01088 in GES-1 cells was higher than that of gastric cancer cell lines; the expression level of LINC01088 in gastric cancer cell line BGC823 was the lowest (p < .01). B The qRT-PCR results showed that the expression of miR-95 in gastric cancer cell lines was higher than that of GES-1; the gastric cancer cell line BGC823 had the highest expression level of miR-95 (p < .01).
Figure 3.
Figure 3.
The regulatory relationship of LINC01088 and miR-95 in BGC823 cell line. A The results of qRT-PCR showed that after BGC823 cells overexpressed LINC01088, LINC01088 in the cells was significantly increased (p < .001). B The results of qRT-PCR showed that after BGC823 cells overexpressed LINC01088, miR-95 was significantly reduced in BGC823 cells (p < .05). C Bioinformatics analysis showed that there was a direct interaction site between LINC01088 and miR-95. D Analysis of dual-luciferase reporter genes showed that LINC01088 can directly regulate the expression of miR-95, which is consistent with the results of bioinformatics. (p < .01).
Figure 4.
Figure 4.
The effect of inhibiting the expression of LINC01088 in BGC823 cell line on the activity, invasion and migration of BGC823 cells. A MTT results showed that the cell viability was significantly reduced after BGC823 cells overexpressed LINC01088 (p < .05). B, C After overexpression of LINC01088 in BGC823 cells, the invasion and migration ability of cells was significantly reduced (p < .05). D, E After overexpression of LINC01088 in BGC823 cells, genes and proteins related to invasion and migration in the cells were significantly changed (*p < .05, **p < .01).
Figure 5.
Figure 5.
The effect of overexpression of miR-95 on the expression of LAST2 in MKN28 cell line. A The predicted results of target gene binding site sequence analysis show that there is a miR-95 binding site in the 3′UTR region of LATS2 mRNA. B The expression of miR-95 was significantly increased after transfection of miR-95 mimics in MKN28 cells (p < .01). C The mRNA and protein expression of LATS2 was significantly reduced after miR-95 mimics transfection (p < .01). D Analysis of dual-luciferase reporter genes showed that miR-95-5p has a direct regulatory effect on LATS2 mRNA (p < .05).
Figure 6.
Figure 6.
The effect of inhibiting miR-95 on the expression of LAST2 in BGC823 cell line. A The results of qRT-PCR showed that the expression of miR-95-5p in BGC823 cells was significantly reduced after miR-95 inhibitor was transfected into BGC823 cells (p < .01). B The expression of LAST mRNA and protein in BGC823 cells was significantly increased after miR-95 inhibitor was transfected (p < .05). C MTT results showed that the activity of BGC823 cells was significantly reduced after miR-95 inhibitor was transfected (p < .05). D, E After BGC823 cells were transfected with miR-95 inhibitor, the cell invasion and migration activity was weakened (p < .05). F, G The mRNA and protein expression of genes related to cell invasion and migration changed after BGC823 cells were transfected with miR-95 inhibitor (*p < .05, **p < .01).
Figure 7.
Figure 7.
Overexpression of LAST2 in the BGC823 cell line affects the viability, invasion and migration of BGC823 cells. A The results of qRT-PCR and Western blot showed that the expression of LAST2 mRNA and protein in BGC823 cells was significantly increased after LAST2 was overexpressed (p < .01). B After overexpression of LAST2 in BGC823 cells, the cell activity was significantly reduced (p < .05). C, D The cell invasion and migration activity was weakened after LAST2 was overexpressed in BGC823 cells (p < .05). E, F The mRNA and protein expressions of genes related to cell invasion and migration changed after overexpression of LAST2 in BGC823 cells (*p < .05, **p < .01).
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