Therapeutic strategies for targeting telomerase in cancer

Chen, Xing; Tang, Wenjian; Shi, Jing; Liu, Ming Ming; Liu, Xinhua

doi:10.1002/med.21626

Cited by 47 publications

(29 citation statements)

References 366 publications

(432 reference statements)

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“…Generally speaking, cancer occurs mainly because cell mutation causes cell abnormal proliferation, usually accompanied by metastasis and spread [28]. The glycolysis metabolism of cells is the key to cellular energy production, which is essential for the normal operation of cells [29].…”

Section: Discussionmentioning

confidence: 99%

Circ_0000140 restrains the proliferation, metastasis and glycolysis metabolism of oral squamous cell carcinoma through upregulating CDC73 via sponging miR-182-5p

Guo

Zhang

2020

Cancer Cell Int

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Background: Oral squamous cell carcinoma (OSCC) is a more common cancer in the world. Emerging evidence suggests that circular RNAs (circRNAs) participate in the progression of OSCC. However, the role of circ_0000140 in OSCC is still unknown. Methods: The expression of circ_0000140 and microRNA-182-5p (miR-182-5p) were assessed by quantitative realtime polymerase chain reaction (qRT-PCR). Also, cell proliferation, migration and invasion were measured by colony formation and transwell assays, respectively. Western blot (WB) analysis was used to test the levels of proliferation, metastasis and glycolysis metabolism-related proteins as well as cell division cycle 73 (CDC73) protein. Further, the extracellular acidification rate (ECAR) of cells was detected by the Seahorse XF Extracellular Flux Analyzer. The lactate acid level of cells was tested by Lactate Assay Kit. Moreover, dual-luciferase reporter was used to verify the interaction between miR-182-3p and circ_0000140 or CDC73, and RNA immunoprecipitation (RIP) assay was employed to further confirm the relationship between miR-182-3p and circ_0000140. In addition, mice xenograft models were built to measure the effect of circ_0000140 on OSCC tumor growth in vivo. Results: Circ_0000140 was lowly expressed in OSCC, and its overexpression hindered proliferation, migration, invasion and glycolysis metabolism in OSCC cells. MiR-182-5p could be sponged by circ_0000140, and its mimic could invert the suppression of circ_0000140 overexpression on OSCC progression. CDC73 could be targeted by miR-182-3p, and its silencing could reverse the inhibition of miR-182-3p inhibitor on OSCC progression. Further, overexpressed circ_0000140 reduced the OSCC tumor growth in vivo. Conclusions: Circ_0000140 might play an anti-cancer role in OSCC, which provided a novel target for clinical therapy of OSCC.

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Section: Discussionmentioning

confidence: 99%

Circ_0000140 restrains the proliferation, metastasis and glycolysis metabolism of oral squamous cell carcinoma through upregulating CDC73 via sponging miR-182-5p

Guo

Zhang

2020

Cancer Cell Int

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“…Telomerase inhibitors remain an attractive approach to target cancer cells, given the specificity of TERT expression in tumor cells [1]. Telomerase inhibition has already been exploited as an anticancer strategy, since it reduces the proliferative potential of cancer cells after continuous cell divisions within the tumor; indeed, several classes of telomerase inhibitors have been developed, most of which specifically affect telomere maintenance [28]. However, the time to antineoplastic effectiveness of telomerase inhibitors depends on the original length of the telomeres of the cancer cells and, apparently, these agents are effective in halting tumor growth only after the cancer cells have shortened their telomeres.…”

Section: Discussionmentioning

confidence: 99%

Anti-Proliferative and Pro-Apoptotic Effects of Short-Term Inhibition of Telomerase In Vivo and in Human Malignant B Cells Xenografted in Zebrafish

Giunco

Zangrossi

Pozzolo

et al. 2020

Cancers

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Besides its canonical role in stabilizing telomeres, telomerase reverse transcriptase (TERT) may promote tumor growth/progression through extra-telomeric functions. Our previous in vitro studies demonstrated that short-term TERT inhibition by BIBR1532 (BIBR), an inhibitor of TERT catalytic activity, negatively impacts cell proliferation and viability via telomeres’ length-independent mechanism. Here we evaluate the anti-proliferative and pro-apoptotic effects of short-term telomerase inhibition in vivo in wild-type (wt) and tert mutant (terthu3430/hu3430; tert−/−) zebrafish embryos, and in malignant human B cells xenografted in casper zebrafish embryos. Short-term Tert inhibition by BIBR in wt embryos reduced cell proliferation, induced an accumulation of cells in S-phase and ultimately led to apoptosis associated with the activation of DNA damage response; all these effects were unrelated to telomere shortening/dysfunction. BIBR treatment showed no effects in tert−/− embryos. Xenografted untreated malignant B cells proliferated in zebrafish embryos, while BIBR pretreated cells constantly decreased and were significantly less than those in the controls from 24 to up to 72 h after xenotransplantation. Additionally, xenografted tumor cells, treated with BIBR prior- or post-transplantation, displayed a significant higher apoptotic rate compared to untreated control cells. In conclusion, our data demonstrate that short-term telomerase inhibition impairs proliferation and viability in vivo and in human malignant B cells xenografted in zebrafish, thus supporting therapeutic applications of TERT inhibitors in human malignancies.

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“…120 Verbascoside from Pedicularis striata could inhibit cancer cell growth and cell cycle in G2/M phase, induce apoptosis and inhibition of telomerase activity and reduced telomere length. 121 It should be noted that not all PhGs exhibit anticancer properties. For example, Kirmizibekmez et al tested the cytotoxic activity of four PhGs (plantainoside D, calceolarioside D, neocalceolarioside D, and lugrandoside) against a series cancer cell lines, namely SH-SY5Y, T98G, A375, HT29, MCF-7, PC3.…”

Section: Anticancer Activitymentioning

confidence: 99%

Therapeutic potential of phenylethanoid glycosides: A systematic review

Georgiev

Cao

et al. 2020

Medicinal Research Reviews

102

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Phenylethanoid glycosides (PhGs) are generally watersoluble phenolic compounds that occur in many medicinal plants. Until June 2020, more than 572 PhGs have been isolated and identified. PhGs possess antibacterial, anticancer, antidiabetic, anti-inflammatory, antiobesity, antioxidant, antiviral, and neuroprotective properties. Despite these promising benefits, PhGs have failed to fulfill their therapeutic applications due to their poor bioavailability. The attempts to understand their metabolic pathways to improve their bioavailability are investigated. In this review article, we will first summarize the number of PhGs compounds which is not accurate in the literature. The latest

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Therapeutic strategies for targeting telomerase in cancer

Cited by 47 publications

References 366 publications

Circ_0000140 restrains the proliferation, metastasis and glycolysis metabolism of oral squamous cell carcinoma through upregulating CDC73 via sponging miR-182-5p

Circ_0000140 restrains the proliferation, metastasis and glycolysis metabolism of oral squamous cell carcinoma through upregulating CDC73 via sponging miR-182-5p

Anti-Proliferative and Pro-Apoptotic Effects of Short-Term Inhibition of Telomerase In Vivo and in Human Malignant B Cells Xenografted in Zebrafish

Therapeutic potential of phenylethanoid glycosides: A systematic review

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