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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

MALAT1 regulated miR-1297 expression and promoted gastric cancer cell proliferation and invasion. a, b CCK8 cell proliferation was performed to detect the cell abilities after MALAT1 down-regulation, and was rescued by miR-1297 inhibitor treatment in MKN45 or MKN28 cells, **P < 0.05. n.s. not statistics significant. c–f Transwell cell invasion assays and analysis were performed to detect the cell abilities after MALAT1 down-regulation, and were rescued by miR-1297 inhibitor treatment in MKN45 or MKN28 cells, **P < 0.05. n.s. not statistics significant. Results were represented as the average ± SD based on 3 independent experiments
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Fig4: MALAT1 regulated miR-1297 expression and promoted gastric cancer cell proliferation and invasion. a, b CCK8 cell proliferation was performed to detect the cell abilities after MALAT1 down-regulation, and was rescued by miR-1297 inhibitor treatment in MKN45 or MKN28 cells, **P < 0.05. n.s. not statistics significant. c–f Transwell cell invasion assays and analysis were performed to detect the cell abilities after MALAT1 down-regulation, and were rescued by miR-1297 inhibitor treatment in MKN45 or MKN28 cells, **P < 0.05. n.s. not statistics significant. Results were represented as the average ± SD based on 3 independent experiments

Mentions: Next, we examined MALAT1 effects on GC cell growth. CCK8 assays revealed that knockdown of significantly reduced the MKN45 and MKN28 cell proliferation abilities, and this reduction could be restored by co-transfecting with si-MALAT1 and miR-1297 inhibitor (Fig. 4a, b). In addition, transwell cell invasion assay also revealed that knockdown of MALAT1 efficiency inhibited the cell invasion abilities in MKN45 or MKN28 cells, and this inhibition could be restored by co-transfecting with si-MALAT1 and miR-1297 inhibitor (Fig. 4c, f). We further identified the underlying effects of HMGB2 on GC cell proliferation. CCK8 cell proliferation was performed to detect the cell growth abilities after HMGB2 silencing. The results showed that cell proliferation abilities were inhibited after HMGB2 silencing in MKN45 cell (Fig. 5a). Moreover, the expression of Proliferating Cell Nuclear Antigens (PCNA) and Ki-67 were inhibited after HMGB2 silencing in MKN45 cell (Fig. 5b, c). Therefore, the results demonstrated that MALAT1 negatively regulated miR-1297 and promote the HMGB2 expression in gastric cancer progression.Fig. 4


Long non-coding RNA MALAT1 drives gastric cancer progression by regulating HMGB2 modulating the miR-1297
MALAT1 regulated miR-1297 expression and promoted gastric cancer cell proliferation and invasion. a, b CCK8 cell proliferation was performed to detect the cell abilities after MALAT1 down-regulation, and was rescued by miR-1297 inhibitor treatment in MKN45 or MKN28 cells, **P < 0.05. n.s. not statistics significant. c–f Transwell cell invasion assays and analysis were performed to detect the cell abilities after MALAT1 down-regulation, and were rescued by miR-1297 inhibitor treatment in MKN45 or MKN28 cells, **P < 0.05. n.s. not statistics significant. Results were represented as the average ± SD based on 3 independent experiments
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC5383984&req=5

Fig4: MALAT1 regulated miR-1297 expression and promoted gastric cancer cell proliferation and invasion. a, b CCK8 cell proliferation was performed to detect the cell abilities after MALAT1 down-regulation, and was rescued by miR-1297 inhibitor treatment in MKN45 or MKN28 cells, **P < 0.05. n.s. not statistics significant. c–f Transwell cell invasion assays and analysis were performed to detect the cell abilities after MALAT1 down-regulation, and were rescued by miR-1297 inhibitor treatment in MKN45 or MKN28 cells, **P < 0.05. n.s. not statistics significant. Results were represented as the average ± SD based on 3 independent experiments
Mentions: Next, we examined MALAT1 effects on GC cell growth. CCK8 assays revealed that knockdown of significantly reduced the MKN45 and MKN28 cell proliferation abilities, and this reduction could be restored by co-transfecting with si-MALAT1 and miR-1297 inhibitor (Fig. 4a, b). In addition, transwell cell invasion assay also revealed that knockdown of MALAT1 efficiency inhibited the cell invasion abilities in MKN45 or MKN28 cells, and this inhibition could be restored by co-transfecting with si-MALAT1 and miR-1297 inhibitor (Fig. 4c, f). We further identified the underlying effects of HMGB2 on GC cell proliferation. CCK8 cell proliferation was performed to detect the cell growth abilities after HMGB2 silencing. The results showed that cell proliferation abilities were inhibited after HMGB2 silencing in MKN45 cell (Fig. 5a). Moreover, the expression of Proliferating Cell Nuclear Antigens (PCNA) and Ki-67 were inhibited after HMGB2 silencing in MKN45 cell (Fig. 5b, c). Therefore, the results demonstrated that MALAT1 negatively regulated miR-1297 and promote the HMGB2 expression in gastric cancer progression.Fig. 4

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