Curcumol inhibits colorectal cancer proliferation by targeting miR-21 and modulated PTEN/PI3K/Akt pathways

Liu, Haowei; Wang, Juan; Tao, Yexing; Li, Xumei; Qin, Jianli; Bai, Zhun; Chi, Bixia; Wei, Yan; Chen, Xu

doi:10.1016/j.lfs.2019.02.049

Cited by 78 publications

(51 citation statements)

References 31 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Noncoding RNAs have received growing attention in recent years as regulators of oncogenic signalling pathways in oral cancer . The lncRNA HOTAIR and miR‐21 are reported to activate PI3K/Akt signalling by targeting PTEN, a tumour suppressor that inhibits PI3K . In this study, AXT downregulated both HOTAIR and miR‐21, underscoring its modulatory effects on the epigenome.…”

Section: Discussionmentioning

confidence: 62%

Astaxanthin inhibits hallmarks of cancer by targeting the PI3K/NF‐κΒ/STAT3 signalling axis in oral squamous cell carcinoma models

et al. 2019

View full text Add to dashboard Cite

Aberrant activation of the PI3K/Akt signalling pathway, a major driving force of diverse cellular processes has been implicated in tumour development and progression. Here, we report that astaxanthin (AXT), a potent antioxidant ketocarotenoid prevents cancer hallmarks by inhibiting PI3K/Akt and the associated downstream NF‐κB and STAT‐3 signalling pathways in SCC131 and SCC4 oral cancer cells as well as in the hamster buccal pouch carcinogenesis model. Using small molecule inhibitors of NF‐κB, STAT‐3 and PI3K and by overexpression of PI3K, we provide evidence to show that AXT inhibits NF‐κB and STAT‐3 signalling and cancer hallmarks by restraining the kinase activity of PI3K/Akt. Additionally, AXT downregulated the noncoding RNAs (ncRNAs), miR‐21 and HOTAIR that influence PI3K/Akt signalling emphasising its modulatory effects on epigenetic regulation. Ethyl cellulose‐based AXT nanoparticles showed greater chemotherapeutic efficacy in the hamster oral carcinogenesis model compared to native AXT. We suggest that AXT prevents cell proliferation, apoptosis evasion, invasion and angiogenesis by intercepting the crosstalk between the PI3K/Akt, NF‐κB and STAT‐3 signalling circuits both in vitro and in vivo. Astaxanthin that abrogates the PI3K/Akt signalling axis, a central hub that orchestrates acquisition of cancer hallmarks is a promising candidate for anticancer drug development.

show abstract

Section: Discussionmentioning

confidence: 62%

Astaxanthin inhibits hallmarks of cancer by targeting the PI3K/NF‐κΒ/STAT3 signalling axis in oral squamous cell carcinoma models

et al. 2019

View full text Add to dashboard Cite

show abstract

“…lncRNA GAS5 regulates the radiosensitivity of A549 cells through the miR-21/PTEN/Akt axis. PTEN is one of the most important target proteins of miR-21, and the miR-21/PTEN/Akt axis has been revealed to play a crucial role in various cellular activities (27)(28)(29)(30). In this experiment, the activation of the PTEN/Akt pathway was also assessed in our experimental model.…”

Section: Overexpression Of Lncrna Gas5 Increases the Radiosensitivitymentioning

confidence: 99%

Long non‑coding RNA GAS5 increases the radiosensitivity of A549 cells through interaction with the miR‑21/PTEN/Akt axis

et al. 2020

View full text Add to dashboard Cite

Radioresistance hinders the therapeutic outcomes of radiotherapy in non-small cell lung cancer (NSCLC). Although long non-coding RNAs (lncRNAs) have been demonstrated to participate in the regulation of multiple cell behaviors, whether they can modulate the radiosensitivity of NSCLC and the underlying molecular mechanisms have not been well investigated. In the present study, it was revealed that NSCLC NCI-H460 cells were more sensitive to ionizing radiation (IR) than A549 cells. Using the RNA-Seq method, four highly differentially expressed lncRNAs were identified, including the growth arrest-specific transcript 5 (GAS5), syntaxin binding protein 5 antisense RNA 1 (STXBP5-AS1), metastasis associated lung adenocarcinoma transcript 1 (MALAT1) and X-inactive specific transcript (XIST), which were predicted to play roles in the acquisition of radiosensitivity. Using real-time quantitative PCR (qPCR), it was demonstrated that lncRNA GAS5 was significantly upregulated in NCI-H460 cells but not in A549 cells during IR. Mechanistically, it was demonstrated that overexpression of lncRNA GAS5 decreased the level of microRNA-21 (miR-21). Overexpression of lncRNA GAS5 or suppression of miR-21 markedly increased the IR-induced cell apoptosis of A549 cells. It was also demonstrated that overexpression of lncRNA GAS5 increased PTEN expression and suppressed Akt phosphorylation through the modulation of miR-21. Notably, it was revealed that IR enhanced the interaction between lncRNA GAS5 and the miR-21/PTEN/Akt axis. In summary, the present findings revealed that lncRNA GAS5 has a radiosensitization effect on NSCLC, indicating the potential application of lncRNA GAS5 in NSCLC radiotherapy.

show abstract

“…The overexpression of miR-21, a characteristic oncomiR, was observed in CRC [25,26]. Increased miR-21 expression is involved in crucial CRC-relevant processes through suppressing PDCD4, TIMP3, and PTEN [27,28]. Hence, miR-21 is an attractive therapeutic target.…”

Section: Discussionmentioning

confidence: 99%

Novel circular RNA hsa_circ_0077837 suppresses colorectal cancer cell proliferation by regulating the microRNA 21/phosphatase and tensin homolog axis

Sheng

Dong

Zhang

et al. 2020

Preprint

View full text Add to dashboard Cite

Background: Circular RNA (circRNA) is a novel noncoding RNA (ncRNA) that assumes critical roles in tumor occurrence and progression. circRNA functions in many tumors as a kind of microRNA (mRNA) “sponge.” The present study sought to investigate the part played by circRNA in colorectal cancer (CRC) progression and to elucidate the relevant action mechanism(s). Methods: We detected lower hsa_circ_0077837 (circEPB41L2) expression in CRC by data analysis based on previous studies. We demonstrated the antitumor part of circEPB41L2 in CRC cells via a group of biological experiments. We subsequently took advantage of pull-down and dual-luciferase reporter assays to recognize circEPB41L2 downstream microRNA 21 (miR-21). Western blotting was conducted to confirm that the circEPB41L2–miR-21–phosphatase and tensin homolog (Pten)/AKT axis is responsible for CRC tumor growth suppression. The antitumor part of circEPB41L2 in vivo was eventually demonstrated by HCT116 xenograft model. Results: We found that circEPB41L2 overexpression inhibited the proliferation of CRC cells. Further, the miR-21 phenocopy suppressed circNRIP1 overexpression, while its overexpression also inhibited the cancer suppressive function of circEPB41L2. circEPB41L2 was confirmed to be able to inhibit tumor growth by enhancing Pten expression. Finally, the antitumor part of circEPB41L2 was confirmed. Conclusions: We demonstrated that circEPB41L2 sponges miR-21 to increase the Pten expression level and consequently serve as a cancer suppressor in CRC.

show abstract

Curcumol inhibits colorectal cancer proliferation by targeting miR-21 and modulated PTEN/PI3K/Akt pathways

Cited by 78 publications

References 31 publications

Astaxanthin inhibits hallmarks of cancer by targeting the PI3K/NF‐κΒ/STAT3 signalling axis in oral squamous cell carcinoma models

Astaxanthin inhibits hallmarks of cancer by targeting the PI3K/NF‐κΒ/STAT3 signalling axis in oral squamous cell carcinoma models

Long non‑coding RNA GAS5 increases the radiosensitivity of A549 cells through interaction with the miR‑21/PTEN/Akt axis

Novel circular RNA hsa_circ_0077837 suppresses colorectal cancer cell proliferation by regulating the microRNA 21/phosphatase and tensin homolog axis

Contact Info

Product

Resources

About