The down-regulated ING5 expression in lung cancer: A potential target of gene therapy

Zhao, Shuang; Shen, Dao-fu; Gao, Yang; Shi, Shuai; Wu, Jicheng; Liu, Hongxu; Sun, Hongzhi; Su, Rongjian; Zheng, Haixue

doi:10.18632/oncotarget.10519

Cited by 16 publications

(35 citation statements)

References 30 publications

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“…In spite of these the correlation between ING5 and ovarian cancer still remained unclear. Various studies reported that ING5 expression was down-regulated or ING5 was a negative regulator of chemoresistance in many kinds of tumors [18, 25–34]. Consistent with these results, we demonstrated that ING5 inhibited cell proliferation, promoted cell apoptosis and inhabited chemoresistance in ovarian cancer.…”

Section: Discussionsupporting

confidence: 90%

“…ING5, one of the ING family genes and as a transcriptional co-activator, has been demonstrated to play important roles in the development of tumor [18, 25–34]. Some studies reported that the decreased ING5 protein and its cytoplasmic translocation were observed in many tumors, including bladder cancer [18], lung cancer [25, 27], oral squamous cell carcinoma [28, 30], head and neck squamous cell carcinoma [31], colorectal [32], pancreatic cancer [29], gastric carcinoma [26, 33] and ameloblastoma [34].…”

Section: Discussionmentioning

confidence: 99%

“…Some studies reported that the decreased ING5 protein and its cytoplasmic translocation were observed in many tumors, including bladder cancer [18], lung cancer [25, 27], oral squamous cell carcinoma [28, 30], head and neck squamous cell carcinoma [31], colorectal [32], pancreatic cancer [29], gastric carcinoma [26, 33] and ameloblastoma [34]. In addition, it was reported that ING5 could affect adhesion, migration, invasion, proliferation and apoptosis of tumor cells [18, 25–34]. Bax and GADD45 were ING5 target apoptotic genes [35, 36].…”

Section: Discussionmentioning

confidence: 99%

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MiR-1307 promotes ovarian cancer cell chemoresistance by targeting the ING5 expression

et al. 2017

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BackgroundWe aimed to investigate the function of miR-1307 in chemoresistance and to explore its chemoresistance mechanism in ovarian cancer.MethodsIC50 determination was used to test the chemoresistance profling in ovarian cancer cells. QRT-PCR or western blot was used to validate the expression level of miR-1307 and candidate gene or protein. Colony formation assay and FITC-labeled enhanced Annexin V immunofluorescence were used to compare cell proliferation and apoptosis ability, respectively. The potential target gene and its biological function of miRNA-1307 were also analyzed. Bioinformatics and Luciferase Reporter Gene Assay were conducted to validate the regulation of miRNA-1307 on the ING5 expression. Xenografts assay was used to demonstrate the inhibiting effect of miR-1307 ASO and Taxol therapy against ovarian cancer in vivo.ResultsMiR-1307 was over-expressed in chemoresistant ovarian cancer cell line A2780/Taxol, and over-expression or loss of miR-1307 promoted or inhabited chemoresistance. And we also found that the over-expression of miR-1307 promoted proliferation and inhibited apoptosis in ovarian cancer cells. Besides, we demonstrated that ING5 was a direct target of miR-1307 and miR-1307 down-regulated the ING5 expression in ovarian cancer cells. Additionally, we showed that ING5 inhibited cell proliferation, promoted cell apoptosis and inhabited chemoresistance reversely. Furthermore, the up-regulated ability of cell apoptosis and down-regulated ability of chemoresistance following the loss of miR-1307 was reversed by adding ING5 siRNA in vitro. Finally, we proved the inhibiting effect of miR-1307 ASO and Taxol therapy by increasing the ING5 expression against ovarian cancer through xenografts assay in vivo.ConclusionOur results suggested that miR-1307 could promote ovarian cancer chemoresistance by targeting the ING5 expression and miR-1307 might serve as a therapeutic target for ovarian cancer.

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Section: Discussionsupporting

confidence: 90%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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MiR-1307 promotes ovarian cancer cell chemoresistance by targeting the ING5 expression

et al. 2017

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“…Reportedly, ING5 was found to repress proliferation, and elevate autophagy and apoptosis in gastric cancer cells [37]. Additionally, ING5 played a suppressive role in proliferation, migration and invasion in lung cancer [38].…”

Section: Discussionmentioning

confidence: 95%

MicroRNA-196b-5p promotes malignant progression of colorectal cancer by targeting ING5

Wang

Chi

et al. 2020

Cancer Cell Int

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Background: miR-196b-5p expression is deregulated in many malignant tumors. Although miR-196b-5p has been implicated in the malignant transformation of colorectal cancer, its role in this specific type of cancer has not been fully explored. Thus, the present study was aimed to examine the cellular function of miR-196b-5p and its role in malignant biological behavior in colorectal cancer. Methods: miR-196b-5p expression was measured in colorectal cancer tissues and cell lines using quantitative real-time PCR. Cell counting kit-8 (CCK-8) assay and Transwell assay were used to detect proliferation, migration, and invasion in cell lines, whereas flow cytometry was applied to study apoptosis. Western blot analysis was performed to measure the protein levels. Dual luciferase reporter assay was used to investigate the interaction between miR-196b-5p and ING5. Tumor formation was evaluated in mice. Results: MiR-196b-5p was abundantly expressed in colorectal cancer tissues and cell lines, whereas ING5 was expressed at low levels. MiR-196b-5p was successfully overexpressed or knocked down in colorectal cancer cells. We found that miR-196b-5p overexpression significantly accelerated the proliferation, cell cycle, migration and invasion, while inhibited cell apoptosis in colorectal cancer cells. However, miR-196b-5p inhibitor showed the opposite effects. Moreover, ING5 overexpression or knockdown was successfully performed in colorectal cancer cells. ING5 overexpression suppressed proliferation, migration, invasion, the phosphorylation of PI3K, Akt as well as MEK, and promoted cell apoptosis, which could be reversed by ING5 knockdown. Additionally, ING5 was identified as a target of miR-196b-5p through bioinformatics analysis and a luciferase activity assay. Furthermore, ING5 knockdown could attenuate the decrease in proliferation, migration, invasion, and the protein levels of p-PI3K, p-Akt, and p-MEK, which were induced by miRNA-196b-5p inhibitor. Besides, miR-196b-5p knockdown inhibited tumor growth, whereas ING5 knockdown elevated it in vivo. Conclusions: In conclusion, miR-196b-5p promotes cell proliferation, migration, invasion, and inhibits apoptosis in colorectal cancer by targeting ING5.

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“…Similar to SAHA treatment, ING5 overexpression was confirmed to lower cell viability, energy metabolism, migration, and invasion and to promote the apoptosis of SH-SY5Y cells, which is consistent with other reports. [41][42][43][44] Furthermore, the same regulatory effects of ING5 were observed on phenotype-related protein expression (eg, acetylhistone upregulation). ING5 can form HAT complexes and subsequently promote histone acetylation.…”

Section: Discussionmentioning

confidence: 99%

ING5‐mediated antineuroblastoma effects of suberoylanilide hydroxamic acid

Jiang

Yang

et al. 2018

Cancer Medicine

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Neuroblastoma is the most common extracranial solid neuroendocrine cancer and is one of the leading causes of death in children. To improve clinical outcomes and prognosis, discovering new promising drugs and targeted medicine is essential. We found that applying Suberoylanilide hydroxamic acid (SAHA; Vorinostat, a histone deacetylase inhibitor) and MG132 (a proteasome inhibitor) to SH‐SY5Y cells synergistically suppressed proliferation, glucose metabolism, migration, and invasion and induced apoptosis and cell cycle arrest. These effects occurred both concentration and time dependently and were associated with the effects observed with inhibitor of growth 5 (ING5) overexpression. SAHA and MG132 treatment increased the expression levels of ING5, PTEN, p53, Caspase‐3, Bax, p21, and p27 but decreased the expression levels of 14‐3‐3, MMP‐2, MMP‐9, ADFP, Nanog, c‐myc, CyclinD1, CyclinB1, and Cdc25c concentration dependently, similar to ING5. SAHA may downregulate miR‐543 and miR‐196‐b expression to enhance the translation of ING5 protein, which promotes acetylation of histones H3 and H4. All three proteins (ING5 and acetylated histones H3 and H4) were recruited to the promoters of c‐myc, Nanog, CyclinD1, p21, and p27 for complex formation, thereby regulating the mRNA expression of downstream genes. ING5 overexpression and SAHA and/or MG132 administration inhibited tumor growth in SH‐SY5Y cells by suppressing proliferation and inducing apoptosis. The expression of acetylated histones H3 and ING5 may be closely linked to the tumor size of neuroblastomas. In summary, SAHA and/or MG132 can synergistically suppress the malignant phenotypes of neuroblastoma cells through the miRNA‐ING5‐histone acetylation axis and via proteasomal degradation, respectively. Therefore, the two drugs may serve as potential treatments for neuroblastoma.

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The down-regulated ING5 expression in lung cancer: A potential target of gene therapy

Cited by 16 publications

References 30 publications

MiR-1307 promotes ovarian cancer cell chemoresistance by targeting the ING5 expression

MiR-1307 promotes ovarian cancer cell chemoresistance by targeting the ING5 expression

MicroRNA-196b-5p promotes malignant progression of colorectal cancer by targeting ING5

ING5‐mediated antineuroblastoma effects of suberoylanilide hydroxamic acid

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