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Long non-coding RNA MALAT1 drives gastric cancer progression by regulating HMGB2 modulating the miR-1297

View Article: PubMed Central - PubMed

ABSTRACT

Background: Emerging evidences have verified that long non-coding RNAs (lncRNAs) play important regulatory roles in the pathogenesis and progression of cancers. lncRNAs metastasis associated lung adenocarcinoma transcript 1 (MALAT1) have been found to be up-regulated in some human cancers. The main objective of this study was to investigate the expression level and biological function of MALAT1 in gastric cancer (GC).

Methods: Quantificational real-time polymerase chain reaction (qRT-PCR) was performed to detect the mRNA levels of MALAT1 in 78 paired gastric carcinoma tissues and adjacent normal tissues, and the associations of MALAT1 expression with the clinicopathological features were analyzed, and the prognosis of gastric carcinoma patients was evaluated. The HMGB2 mRNA and protein expressions were detected by qRT-PCR and western-blot analysis. Luciferase reporter assay was used to determine miR-1297 was a target of MALAT1.

Results: In this study, we demonstrated MALAT1 was up-regulation in GC tissues compared with adjacent normal tissues and higher MALAT1 expression was correlated with local invasion, lymph node metastasis and TNM stage. Patients with higher MALAT1 expression predicted a shorter survival and poor prognosis. Functionally, we revealed that MALAT1 promoted cells proliferation and invasion in GC. Mechanistically, our results demonstrated that MALAT1 was negatively correlation with miR-1297 and functioned as a molecular sponging miR-1297, antagonizing its ability to suppress HMGB2 expression.

Conclusions: Taken together, these results demonstrated that MALAT1/miR-1297/HMGB2 axis acted as critical regulator pathway in GC tumorigenesis and progression, which provided a novel therapeutic target for gastric cancer.

No MeSH data available.


Related in: MedlinePlus

Up-regulation of MALAT1 in tumor tissues samples and cell lines. a The MALAT1 expression in 78 pairs of gastric cancer and corresponding non-cancerous gastric tissues was detected by qRT-PCR assays. **P < 0.05, the internal control was GAPDH. b Kaplan–Meier survival curve and log-rank test was perform to analyze the correlation between MALAT1 expression and the over survival (OS) time. c The MALAT1 expression in gastric cancer cells and an immortalized normal gastric epithelial cell line GES-1 was detected by qRT-PCR assays. **P < 0.05. d, e The MALAT1 expression in MKN45 or MKN28 cells was detected after knockdown of MALAT1 by qRT-PCR assays. Results were represented as the average ± SD based on 3 independent experiments. **P < 0.05
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Fig1: Up-regulation of MALAT1 in tumor tissues samples and cell lines. a The MALAT1 expression in 78 pairs of gastric cancer and corresponding non-cancerous gastric tissues was detected by qRT-PCR assays. **P < 0.05, the internal control was GAPDH. b Kaplan–Meier survival curve and log-rank test was perform to analyze the correlation between MALAT1 expression and the over survival (OS) time. c The MALAT1 expression in gastric cancer cells and an immortalized normal gastric epithelial cell line GES-1 was detected by qRT-PCR assays. **P < 0.05. d, e The MALAT1 expression in MKN45 or MKN28 cells was detected after knockdown of MALAT1 by qRT-PCR assays. Results were represented as the average ± SD based on 3 independent experiments. **P < 0.05

Mentions: To investigate the MALAT1 expression in 78 paired GC tissues and adjacent non-cancer tissues, qRT-PCR analysis was applied. The results demonstrated that the expression of MALAT1 in GC tissues was up-regulated compared to the paired adjacent non-cancer tissues (Fig. 1a). We then analyzed the correlation between MALAT1 and Clinicopathological factors. As shown in Table 1, the result showed that MALAT1 expression was significantly correlation with local invasion, lymph node metastasis and TNM stage. Furthermore, we demonstrated that patients with higher MALAT1 expression had a shorter survival time in GC patients (Log-rank = 23.94, P < 0.001, Fig. 1b). As shown in Fig. 1c, we also demonstrated that MALAT1 expression was also significantly higher in four cell lines compared with that in GES-1 cells. The siRNA-2 was used to perform to silence the MALAT1 expression in the following experiences, according to knockout efficiency in the MKN45 and MKN28 cells (Fig. 1d, e).Fig. 1


Long non-coding RNA MALAT1 drives gastric cancer progression by regulating HMGB2 modulating the miR-1297
Up-regulation of MALAT1 in tumor tissues samples and cell lines. a The MALAT1 expression in 78 pairs of gastric cancer and corresponding non-cancerous gastric tissues was detected by qRT-PCR assays. **P < 0.05, the internal control was GAPDH. b Kaplan–Meier survival curve and log-rank test was perform to analyze the correlation between MALAT1 expression and the over survival (OS) time. c The MALAT1 expression in gastric cancer cells and an immortalized normal gastric epithelial cell line GES-1 was detected by qRT-PCR assays. **P < 0.05. d, e The MALAT1 expression in MKN45 or MKN28 cells was detected after knockdown of MALAT1 by qRT-PCR assays. Results were represented as the average ± SD based on 3 independent experiments. **P < 0.05
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Related In: Results  -  Collection

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Fig1: Up-regulation of MALAT1 in tumor tissues samples and cell lines. a The MALAT1 expression in 78 pairs of gastric cancer and corresponding non-cancerous gastric tissues was detected by qRT-PCR assays. **P < 0.05, the internal control was GAPDH. b Kaplan–Meier survival curve and log-rank test was perform to analyze the correlation between MALAT1 expression and the over survival (OS) time. c The MALAT1 expression in gastric cancer cells and an immortalized normal gastric epithelial cell line GES-1 was detected by qRT-PCR assays. **P < 0.05. d, e The MALAT1 expression in MKN45 or MKN28 cells was detected after knockdown of MALAT1 by qRT-PCR assays. Results were represented as the average ± SD based on 3 independent experiments. **P < 0.05
Mentions: To investigate the MALAT1 expression in 78 paired GC tissues and adjacent non-cancer tissues, qRT-PCR analysis was applied. The results demonstrated that the expression of MALAT1 in GC tissues was up-regulated compared to the paired adjacent non-cancer tissues (Fig. 1a). We then analyzed the correlation between MALAT1 and Clinicopathological factors. As shown in Table 1, the result showed that MALAT1 expression was significantly correlation with local invasion, lymph node metastasis and TNM stage. Furthermore, we demonstrated that patients with higher MALAT1 expression had a shorter survival time in GC patients (Log-rank = 23.94, P < 0.001, Fig. 1b). As shown in Fig. 1c, we also demonstrated that MALAT1 expression was also significantly higher in four cell lines compared with that in GES-1 cells. The siRNA-2 was used to perform to silence the MALAT1 expression in the following experiences, according to knockout efficiency in the MKN45 and MKN28 cells (Fig. 1d, e).Fig. 1

View Article: PubMed Central - PubMed

ABSTRACT

Background: Emerging evidences have verified that long non-coding RNAs (lncRNAs) play important regulatory roles in the pathogenesis and progression of cancers. lncRNAs metastasis associated lung adenocarcinoma transcript 1 (MALAT1) have been found to be up-regulated in some human cancers. The main objective of this study was to investigate the expression level and biological function of MALAT1 in gastric cancer (GC).

Methods: Quantificational real-time polymerase chain reaction (qRT-PCR) was performed to detect the mRNA levels of MALAT1 in 78 paired gastric carcinoma tissues and adjacent normal tissues, and the associations of MALAT1 expression with the clinicopathological features were analyzed, and the prognosis of gastric carcinoma patients was evaluated. The HMGB2 mRNA and protein expressions were detected by qRT-PCR and western-blot analysis. Luciferase reporter assay was used to determine miR-1297 was a target of MALAT1.

Results: In this study, we demonstrated MALAT1 was up-regulation in GC tissues compared with adjacent normal tissues and higher MALAT1 expression was correlated with local invasion, lymph node metastasis and TNM stage. Patients with higher MALAT1 expression predicted a shorter survival and poor prognosis. Functionally, we revealed that MALAT1 promoted cells proliferation and invasion in GC. Mechanistically, our results demonstrated that MALAT1 was negatively correlation with miR-1297 and functioned as a molecular sponging miR-1297, antagonizing its ability to suppress HMGB2 expression.

Conclusions: Taken together, these results demonstrated that MALAT1/miR-1297/HMGB2 axis acted as critical regulator pathway in GC tumorigenesis and progression, which provided a novel therapeutic target for gastric cancer.

No MeSH data available.


Related in: MedlinePlus