LncRNA HEIH Enhances Paclitaxel-Tolerance of Endometrial Cancer Cells via Activation of MAPK Signaling Pathway

Guo, Jinxin; Tang, Tian; Li, Jinhong; Yang, Yihong; Zhang, Long; Quan, Yi

doi:10.1007/s12253-019-00718-w

Cited by 31 publications

(26 citation statements)

References 28 publications

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“… 7 Increasing evidence has shown that aberrant expression of lncRNAs is in association with the development and prognosis of EC, such as MALAT1, GAS5, CCAT2, and HEIH. 8 - 11 HOX genes code for proteins that function as critical master regulatory transcription factors during embryogenesis, and several HOX genes are associated with oncogenesis. 12 Many HOX genes, such as HOXB9, HOXB13, HOXA10, and HOTAIR, have demonstrated abnormal expression in EC tissues and cells.…”

Section: Introductionmentioning

confidence: 99%

RETRACTED: Long Noncoding RNA HOXB-AS1 Is Upregulated in Endometrial Carcinoma and Sponged miR-149-3p to Upregulate Wnt10b

Qiu

Jiang

et al. 2020

Technol Cancer Res Treat

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The functions of Long noncoding RNA (lncRNA) HOXB-AS1 have been investigated in glioblastoma and multiple myeloma. However, the role of lncRNA HOXB-AS1 in endometrial carcinoma (EC) remains largely unknown. This study investigated the underlying mechanisms of the lncRNA HOXB-AS1 on the progression of EC. In this study, We found that HOXB-AS1 expression was significantly upregulated in EC tissue samples and was associated with shorter survival time. Furthermore, upregulation of HOXB-AS1 promoted proliferation, invasion, and migration of EC cell. HOXB-AS1 and Wnt10b directly bound to miR-149-3p. HOXB-AS1 increased the expression of Wnt10b by binding to miR-149-3p. We further verified the upregulation of β-catenin, cyclin D1, and c-myc induced by HOXB-AS1. In conclusion, our results indicated that HOXB-AS1 exerted oncogenic function as competing endogenous RNA (ceRNA) of miR-149-3p to release Wnt10b and activated Wnt/β-catenin pathway.

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Section: Introductionmentioning

confidence: 99%

RETRACTED: Long Noncoding RNA HOXB-AS1 Is Upregulated in Endometrial Carcinoma and Sponged miR-149-3p to Upregulate Wnt10b

Qiu

Jiang

et al. 2020

Technol Cancer Res Treat

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“…siRNA targeting p38 MAPK and its scramble control were purchased from the Shanghai Genepharma Company. The transfection was performed as previously described (21). Cells were passaged at a density of 70% and transfected with Lipofectamine 3000 reagent (Life Technologies) on the following day according to the manufacturer's instructions.…”

Section: Cell Transfectionmentioning

confidence: 99%

LIMD1 Increases the Sensitivity of Lung Adenocarcinoma Cells to Cisplatin via the GADD45α/p38 MAPK Signaling Pathway

Zeng

Wang

et al. 2020

Front. Oncol.

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Objective: To investigate the effect of LIM domain-containing protein 1 (LIMD1) on the sensitivity of lung adenocarcinoma cells to cisplatin and explore the mechanism. Methods: A549 and H1299 cells were transfected with lentivirus to establish LIMD1-overexpressing cell lines and their respective controls. The protein expression of DNA damage-inducible 45 alpha (GADD45α) and p38 mitogen-activated protein kinase (MAPK) was detected by Western blot. The survival of A549-vec, A549-LIMD1, H1299-vec, and H1299-LIMD1 cells after cisplatin treatment was observed by CCK-8, and the viability was calculated accordingly. Then, SB203580 was used to inhibit the activity of the p38 MAPK signaling pathway, after which the survival of A549-vec, A549-LIMD1, H1299-vec, and H1299-LIMD1 cells in response to cisplatin was observed again by CCK-8, and the viability was calculated accordingly. Results: When LIMD1 was overexpressed in A549 and H1299 cells, the levels of GADD45α and p-p38 MAPK were increased, but total p38 MAPK expression showed no significant change. After adding 30 µM cisplatin, the optical density (OD) values of A549-LIMD1 and H1299-LIMD1 cells were significantly lower than those of their respective controls at 24, 48, and 72 h. The viability of A549-LIMD1 and H1299-LIMD1 cells was significantly lower than that of their respective controls at all the times tested (p < 0.05). The Western blot results showed that the expression of apoptotic proteins cleaved caspase 3 and cleaved PARP in cisplatin-treated A549-LIDM1 and H1299-LIMD1 cells was significantly higher than that in their respective control cells. Flow cytometry showed that the apoptosis rates of A549-LIMD1 and H1299-LIMD1 cells were significantly higher than those of their respective controls (p < 0.05). SB203580 significantly inhibited the activation of the p38 MAPK signaling pathway in lung adenocarcinoma cells; however, neither the OD values nor the viability of A549-LIMD1 cells and H1299-LIMD1 cells showed no significant difference from those of their controls at 24, 48, and 72 h after cisplatin and SB203580 treatment (p > 0.05 for both). Western blot analysis showed that after SB203580 was added, the expression of cleaved caspase 3 and cleaved PARP in Zeng et al. LIMD1 Increases Sensitivity by GADD45α/p38 MAPK A549-LIMD1 and H1299-LIMD1 cells presented no significant difference compared with that in their respective controls. Conclusion: LIMD1 increases the sensitivity of lung adenocarcinoma cells to cisplatin by activating the GADD45α/p38 MAPK signaling pathway.

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“…Several studies have previously demonstrated that lncRNAs are involved in drug resistance of GC (Yang et al, 2015;Ayers and Vandesompele, 2017;Heery et al, 2017). Guo et al (2019) reported that downregulation of lncRNA-HEIH reversed paclitaxel resistance of endometrial cancer cells by activation of the MAPK signaling pathway. Based on these conclusions, the effect of HEIH expression was explored on oxaliplatin sensitivity in GC cells by the SRB assay.…”

Section: Discussionmentioning

confidence: 99%

LncRNA-HEIH is a Novel Diagnostic and Predictive Biomarker in Gastric Cancer

Chen

Sun

et al. 2021

Genetic Testing and Molecular Biomarkers

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Background: Gastric cancer (GC) is associated with a high mortality rate. Long noncoding RNA (lncRNA)high expression in hepatocellular carcinoma (HEIH) has recently gained interest as a marker for the detection of several cancer types. This study was designed to uncover the function of lncRNA-HEIH in GC. Materials and Methods: Oncomine was used to analyze HEIH expression in cancerous and paired noncancerous tissues of GC patients. Subsequently, the expression levels of HEIH in GC cells was determined by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). In addition, the effects of HEIH expression level on clinicopathological parameters and prognosis were further studied by statistical analysis and Kaplan-Meier survival curves. GC cell proliferation and the influence of HEIH on the sensitivity of cells to oxaliplatin following HEIH knockdown were assessed using sulforhodamine blue (SRB) assays in the MKN45 and AGS cell lines. In addition, the expression levels of p53 were detected by RT-qPCR following knockdown of HEIH. Results: The lncRNA-HEIH was highly expressed in both GC tissues and GC cell lines. Patients with high HEIH expression were associated with medium-high differentiation ( p = 0.0058), distant metastasis (M, p = 0.0378), lymph node metastasis (N, p = 0.0083), and a deeper tumor invasion (T, p = 0.0204). Elevated expression levels of HEIH in GC patients were associated with a worse prognosis compared to GC patients with low HEIH expression. This finding was supported by the parameters of overall survival ( p = 3.3e-06), first progression ( p = 0.00028), and postprogression ( p = 1.5e-08). Downregulation of HEIH expression inhibited cell proliferation, enhanced oxaliplatin sensitivity, and induced the expression of p53 in MKN45 and AGC cells. Conclusion: These findings provide evidence that HEIH may be useful as a prognostic biomarker in GC. This lncRNA may also serve as a potential therapeutic target in GC patients.

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LncRNA HEIH Enhances Paclitaxel-Tolerance of Endometrial Cancer Cells via Activation of MAPK Signaling Pathway

Cited by 31 publications

References 28 publications

RETRACTED: Long Noncoding RNA HOXB-AS1 Is Upregulated in Endometrial Carcinoma and Sponged miR-149-3p to Upregulate Wnt10b

RETRACTED: Long Noncoding RNA HOXB-AS1 Is Upregulated in Endometrial Carcinoma and Sponged miR-149-3p to Upregulate Wnt10b

LIMD1 Increases the Sensitivity of Lung Adenocarcinoma Cells to Cisplatin via the GADD45α/p38 MAPK Signaling Pathway

LncRNA-HEIH is a Novel Diagnostic and Predictive Biomarker in Gastric Cancer

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