Vitamin D Enhances the Efficacy of Irinotecan through miR-627–Mediated Inhibition of Intratumoral Drug Metabolism

Sun, Meiyan; Zhang, Qunshu; Yang, Xiaoyu; Qian, Steven Y.; Guo, Bin

doi:10.1158/1535-7163.mct-16-0095

Cited by 32 publications

(29 citation statements)

References 43 publications

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“…Although it seems that MK1775 monotherapy could achieve an anticancer effect in p53 mutant colonic cancer cells, the dosage for treatment is still a challenge, as the toxicity of agents targeting the cell cycle checkpoint is big problem. Combination with other chemotherapy drugs is a better choice as a first-line chemotherapy regime in metastatic colonic cancer (25), and a number of studies are seeking the proper strategy to increase the sensitivity of cancer cells to the cytotoxicity effect (26)(27)(28). In the present study MK1775 was demonstrated to increase the sensitivity of cells to the effect of irinotecan both in HT29 and SW480, and resulting in increased γ-H2AX and cleaved-caspase 3.…”

Section: Discussionmentioning

confidence: 52%

Wee1 inhibition can suppress tumor proliferation and sensitize p53 mutant colonic cancer cells to the anticancer effect of irinotecan

et al. 2017

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Wee1 is an oncogenic nuclear kinase, which can regulate the cell cycle as a crucial G2M checkpoint. Overexpression of Wee1 can be observed in various cancer types, which may lead to a poor prognosis, but the potential therapeutic value of Wee1 in colorectal cancer has not been fully studied. In the present study, the role of Wee1 in colonic cancer was investigated. Wee1 inhibition by small interfering RNA was demonstrated to significantly restrain cancer cell proliferation and sensitize the p53 mutant colonic cancer cell lines HT29 and SW480 to the effect of treatment with ionizing radiation. The anticancer effect of the Wee1 inhibitor MK1775 was investigated in these two colonic cancer cell lines. MK1775 was demonstrated to induce significant DNA damage, suppress cell viability and induce apoptosis. In addition, MK1775 sensitized HT29 and SW480 cells to the effect of irinotecan. Annexin V/propidium iodide staining demonstrated that combination therapy can induce increased apoptosis compared with MK1775 or irinotecan monotherapy. The results of western blot analysis also indicated increased expression of the DNA damage marker histone H2AX, and apoptosis‑associated protein cleaved caspase 3, in HT29 and SW480 cells. In conclusion, the present study indicated that Wee1 may be a valuable target for treatment of p53 mutant colonic cancer.

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Section: Discussionmentioning

confidence: 52%

Wee1 inhibition can suppress tumor proliferation and sensitize p53 mutant colonic cancer cells to the anticancer effect of irinotecan

et al. 2017

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“…No published data exists so far on the interaction between irinotecan and SATB2. Irinotecan is inactivated by cytochrome P450 3A4 (CYP3A4), whose activity can be reduced by miRNA [25]. Since miRNAs are known targets of SATB2, an indirect effect on irinotecan efficacy can be surmised.…”

Section: Discussionmentioning

confidence: 99%

Metastatic colorectal carcinomas with high SATB2 expression are associated with better prognosis and response to chemotherapy: a population-based Scandinavian study

et al. 2019

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Background: Survival and response to therapy in patients with metastatic colorectal cancer (mCRC) are very heterogeneous. There is an unmet need for better markers of prognosis and treatment benefit for mCRC patients. The homeobox 2 gene SATB2 has a highly specific expression in colorectal tissue and is associated with better prognosis in non-metastatic CRC. Material and methods: A population-based cohort of 798 mCRC patients was analysed. From primary tumour material, protein expression was assessed by immunohistochemistry. BRAF and KRAS mutation status was also determined. Associations with clinicopathological data, overall and progression-free survival and response to first-line chemotherapy were analysed. Results: Tumour tissue and clinical data were available from 467 patients. SATB2 was strongly expressed in 58% of cases, significantly more in left-sided, low-grade and wild-type BRAF tumours. Patients with high SATB2 tumours had longer overall survival compared with low SATB2 tumours (median 13 vs 8 months respectively, p < .001). Chemotherapy was given to 282 patients (63%). Patients with high SATB2 tumours had longer OS (median 22 vs 15 months respectively, p ¼ .001) and more often responded to chemotherapy than those with low SATB2 (objective response 43% vs 29%, p ¼ .02; clinical response 83% vs 67%, p ¼ .004). Progression-free survival on first-line irinotecan chemotherapy was longer in high SATB2 cases (median 8 vs 4 months respectively, p ¼ .019). Patients with both low SATB2 expression and mutated BRAF (n ¼ 69) had particularly poor survival compared to the rest (median 8 and 12 months respectively, p ¼ .001). In multivariable analysis, the SATB2 findings were independent of known clinicopathological prognostic markers, including BRAF mutation status. Conclusion: Patients with mCRC expressing high level of SATB2 have better prognosis and response to chemotherapy than those with low SATB2 expression. Patients with both low SATB2 expression and mutated BRAF had particularly poor prognosis and could thus benefit from more aggressive therapies.

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“…These observations indicated a tumour suppressive role of miR‐627‐5p in HCC. miR‐627‐5p functions as a tumour suppressor in CRC by targeting JMJD1A and CYP3A4 . Meanwhile, miR‐627‐5p exerts the tumour suppressive role in GBM via attenuating CDK6 and SOX‐2 .…”

Section: Discussionmentioning

confidence: 99%

“…Moreover, miR‐671‐5p and miR‐204 mediate hypoxia‐induced HCC progression via regulating vasodilator stimulated phosphoprotein (VASP) and tuftelin 1 (TUFT1), respectively . MiR‐627‐5p has been previously recognized as a tumour suppressor in colorectal cancer (CRC) and glioblastoma multiforme (GBM) . Vitamin D‐induced miR‐627‐5p inhibits the proliferation of CRC cells by repressing Jumonji domain containing 1A (JMJD1A) .…”

Section: Introductionmentioning

confidence: 99%

“…Vitamin D‐induced miR‐627‐5p inhibits the proliferation of CRC cells by repressing Jumonji domain containing 1A (JMJD1A) . Furthermore, vitamin D‐activated miR‐627‐5p inversely regulates cytochrome P450 family 3 subfamily A member 4 (CYP3A4) expression and subsequently enhances the chemosensitivity to Irinotecan in CRC cells . Additionally, miR‐627‐5p, which is regulated by small nucleolar RNA host gene 15 (SNHG15), represses the expressions of cyclin dependent kinase 6 (CDK6) and SRY‐box transcription factor 2 (SOX‐2) to suppress the tumorigenesis of GBM .…”

Section: Introductionmentioning

confidence: 99%

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MicroRNA‐627‐5p inhibits the proliferation of hepatocellular carcinoma cells by targeting BCL3 transcription coactivator

Wang

Chen

Wang

et al. 2019

Clin Exp Pharma Physio

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Hepatocellular carcinoma (HCC) is a common malignant tumour. An increasing number of studies indicate that microRNAs (miRNAs) are critical regulators in the carcinogenesis and progression of HCC. MiR-627-5p has been identified as a tumour suppressor in colorectal cancer and glioblastoma multiforme. However, the function of miR-627-5p in HCC progression remains unclear yet. In our present study, miR-627-5p was determined to be low-expressed in HCC tissues and cell lines. Furthermore, miR-627-5p was expressed at significantly lower levels in HCC tissues with tumour size >5 cm or advanced tumour stages (III+IV). Additionally, HCC patients with low miR-627-5p level had a significantly poorer overall survival. Functionally, ectopic expression of miR-627-5p obviously inhibited the proliferation, and induced G1 phase arrest and apoptosis of Hep3B and SMMC-7721 cells. Conversely, miR-627-5p silencing facilitated HCC cell proliferation, cell cycle progression and apoptosis resistance. In vivo experiments further confirmed that miR-627-5p overexpression repressed the growth of Hep3B cells in mice. Mechanistically, BCL3 transcription coactivator was predicted as a direct target of miR-627-5p. MiR-627-5p overexpression reduced, whereas miR-627-5p knockdown enhanced the expression of BCL3 protein in HCC cells. Luciferase reporter assay confirmed the direct binding between miR-627-5p and 3′UTR of BCL3.The expression of BCL3 protein was negatively correlated with miR-627-5p level in HCC tissues. More importantly, re-expression of BCL3 partially reversed miR-627-5p induced inhibitory effects on Hep3B cells. In conclusion, these results demonstrated that miR-627-5p functioned as a tumour suppressor in HCC possibly by attenuating BCL3. This finding might offer a new therapeutic target for HCC treatment. K E Y W O R D SBCL3, hepatocellular carcinoma, miR-627-5p, proliferation, tumour growth

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Vitamin D Enhances the Efficacy of Irinotecan through miR-627–Mediated Inhibition of Intratumoral Drug Metabolism

Cited by 32 publications

References 43 publications

Wee1 inhibition can suppress tumor proliferation and sensitize p53 mutant colonic cancer cells to the anticancer effect of irinotecan

Wee1 inhibition can suppress tumor proliferation and sensitize p53 mutant colonic cancer cells to the anticancer effect of irinotecan

Metastatic colorectal carcinomas with high SATB2 expression are associated with better prognosis and response to chemotherapy: a population-based Scandinavian study

MicroRNA‐627‐5p inhibits the proliferation of hepatocellular carcinoma cells by targeting BCL3 transcription coactivator

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