Over-expression of Sirt1 contributes to chemoresistance and indicates poor prognosis in serous epithelial ovarian cancer (EOC)

Shuang, Ting; Wang, Min; Zhou, Yingying; Shi, Cong

doi:10.1007/s12032-015-0706-8

Cited by 44 publications

(44 citation statements)

References 22 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…28 Conversely, Chen et al 50 indicated that miR-181a sensitized human malignant glioma cells to radiation; however, the role of miR-181a in human glioma chemoresistance, and more importantly, the downstream target and regulation mechanism that miR-181a regulated human glioma tumorigenesis, still needed more exploration. 33,34 Our sample analysis identified that the expression of miR-181a was lower in tumors than nontumor tissues. 30,35,37,42 These effects have been linked to cell behaviors, involving cell growth, differentiation, migration, and survival.…”

Section: Discussionmentioning

confidence: 97%

Circular RNA hsa_circ_0076248 promotes oncogenesis of glioma by sponging miR‐181a to modulate SIRT1 expression

Lei

Huang

Zhou

et al. 2018

J of Cellular Biochemistry

View full text Add to dashboard Cite

Glioma is one of the most common primary malignancies of the central nervous system, which has aggressive clinical behavior and a poorer prognosis. MicroRNAs (miRs) are a class of small noncoding RNAs that function as mediators of gene expression, which can be sponged by circRNA provided with a closed circular structure. Dysregulations of circular RNAs (circRNAs) and miRs have been implicated in the development and progression of glioma. In the current study, we investigated the role of circular RNA hsa_circ_0076248 in mediating the oncogenesis of glioma by sponging miR‐181a to modulate silent information regulator 1 (SIRT1) expression in vitro and in vivo. The quantitative real‐time polymerase chain reaction results showed that the expression of miR‐181a was significantly decreased in glioma tissues and cell lines compared with normal brain tissues and normal gliocyte, respectively, and the expression of hsa_circ_0076248 and SIRT1 demonstrated the opposite. Bioinformatics analysis identified hsa_circ_0076248 could sponge miR‐181a, and miR‐181a could target the mRNA of SIRT1. Our results verified that downregulating hsa_circ_0076248 or upregulating miR‐181a could depress the proliferation and invasion of glioma in vitro and in vivo. The experiment also showed that downregulating hsa_circ_0076248 or upregulating miR‐181a could remarkably promote the temozolomide chemotherapy sensitivity. Furthermore, Western blot analysis testified that downregulating hsa_circ_0076248 or upregulating miR‐181a could promote the expression of p53 and SIRT1. In summary, our study sheds light on the regulatory mechanism of hsa_circ_0076248 in glioma growth and invasion via sponging miR‐181a, which downregulates the SIRT1 expression and also suggests that hsa_circ_0076248, miR‐181a, and SIRT1 may serve as potential therapeutic targets for glioma.

show abstract

Section: Discussionmentioning

confidence: 97%

Circular RNA hsa_circ_0076248 promotes oncogenesis of glioma by sponging miR‐181a to modulate SIRT1 expression

Lei

Huang

Zhou

et al. 2018

J of Cellular Biochemistry

View full text Add to dashboard Cite

show abstract

“…It has been suggested that a decline in energy metabolism may play an important role in activating the cell death pathway and dysregulation of pyruvate kinase M2 (PKM2), which favor both carcinogenesis and the Warburg effect [17]. Previous study demonstrated that SIRT1 overexpression is associated with poor outcome and chemo-resistance in ovarian cancer of epithelial origin over-expression, and one of the mechanisms may involve the dysregulation of energy metabolism and stress response [16,18].…”

Section: Introductionmentioning

confidence: 99%

A new SIRT1 inhibitor, MHY2245, induces autophagy and inhibits energy metabolism via PKM2/mTOR pathway in human ovarian cancer cells

Tae¹,

Son²,

Lee³

et al. 2020

Int. J. Biol. Sci.

View full text Add to dashboard Cite

Ovarian cancer is a common gynecological cancer that is found worldwide. Class III histone deacetylase (HDAC) inhibitors, a new class of anticancer agents, induce autophagy in various human cancer cells. The aim of the present study was to investigate the antitumor activity of MHY2245, a new synthetic SIRT inhibitor, on human ovarian cancer cells. We found that MHY2245 exhibited potent cytotoxicity to SKOV3 cells in a time-and concentration-dependent manner. The cytotoxicity of MHY2245 (IC 50 =0.32 µM) was higher than that of doxorubicin (DOX, IC 50 =1.38µM) against SKOV3 cells. MHY2245 significantly inhibited SIRT1 enzyme activity, reduced the expression of SIRT1, increased cell cycle arrest at G 2 /M phase, and induced apoptotic cell death in SKOV3 cells via expression of cytochrome c, cleaved-PARP, cleaved caspase-3, and Bax. This might be associated with blocking of the pyruvate kinase M2 (PKM2)/mTOR pathway. MHY2245 also inhibited tumor growth and reduced tumor size when SKOV3 cells were transplanted into nude mice. Our results indicate that MHY2245 exerts antitumor activity against ovarian cancer cells by blocking the PKM2/mTOR pathway. We suggest that MHY2245 is a promising anticancer agent that disrupts ovarian cancer cell metabolism.

show abstract

“…Furthermore, patients with SIRT1-positive liver cancer have a lower survival rate than those with SIRT1-negative liver cancer (38). Overexpression of SIRT1 has been demonstrated to contribute to chemoresistance in serous epithelial ovarian cancer, where it may be a potential prognostic indicator for patient survival outcome (39). SIRT1 is one among other genes involved in DNA repair that are upregulated in platinum-resistant epithelial ovarian cancer (40).…”

Section: Discussionmentioning

confidence: 99%

MicroRNA‑29c restores cisplatin sensitivity in liver cancer through direct inhibition of sirtuin 1 expression

Zhang

Luo

2018

Oncol Lett

View full text Add to dashboard Cite

Liver cancer is one of the most prevalent human tumors in the world. Despite recent advances regarding the understanding of the molecular basis of liver cancer and the introduction of novel chemotherapeutic approaches, liver cancer remains associated with a poor prognosis. Sirtuin 1 (SIRT1) was identified to be abnormally upregulated in liver cancer. Dysregulation of microRNAs (miRs/miRNAs) is associated with a variety of types of cancer, and miRNAs may also serve a role in tumorigenesis and progression. The present study demonstrated that following the selection of the cisplatin chemoresistant HepG2 cell line, miR-29c is downregulated using reverse transcription-quantitative polymerase chain reaction. Furthermore, overexpression of miR-29c in cisplatin-resistant cancer cells was demonstrated to inhibit tumor cell proliferation and to promote apoptosis and, as well as restoring cisplatin chemosensitivity by using a cell counting assay, colony formation assay, Annexin V-fluorescein isothocyanate/propidium iodide apoptosis analysis, terminal deoxynucleotidyl transferase dUTP nick end labeling and xenograft tumors in nude mice. Mechanistically, according to bioinformatics analysis and a luciferase assay, miR-29c may directly target SIRT1 mRNA and repress SIRT1 expression, which is positively associated with the chemoresistance of liver cancer and may ultimately provide a novel therapeutic method.

show abstract

Over-expression of Sirt1 contributes to chemoresistance and indicates poor prognosis in serous epithelial ovarian cancer (EOC)

Cited by 44 publications

References 22 publications

Circular RNA hsa_circ_0076248 promotes oncogenesis of glioma by sponging miR‐181a to modulate SIRT1 expression

Circular RNA hsa_circ_0076248 promotes oncogenesis of glioma by sponging miR‐181a to modulate SIRT1 expression

A new SIRT1 inhibitor, MHY2245, induces autophagy and inhibits energy metabolism via PKM2/mTOR pathway in human ovarian cancer cells

MicroRNA‑29c restores cisplatin sensitivity in liver cancer through direct inhibition of sirtuin 1 expression

Contact Info

Product

Resources

About