MiR-199a-5p and miR-375 affect colon cancer cell sensitivity to cetuximab by targeting PHLPP1

Mussnich, Paula; Rosa, Roberta; Bianco, Roberto; Fusco, Alfredo; D'Angelo, Daniela

doi:10.1517/14728222.2015.1057569

Cited by 61 publications

(46 citation statements)

References 33 publications

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“…[29][30][31] Liu et al demonstrated miR-451a sensitized breast cancer to Tamoxifen and inhibited growth of breast cancer cells. In addition, Mussnich et al 32 illustrated miR-199a-5p and miR-375 reduced colon cancer sensitive to CTX. Our results showed the expression of miR-551a was up-regulated in the SKOV3 cells treated with DMC.…”

Section: Discussionmentioning

confidence: 98%

Demethoxycurcumin inhibited human epithelia ovarian cancer cells’ growth via up-regulating miR-551a

Sha²

2017

Tumour Biol.

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Curcumin is a natural agent that has ability to dampen tumor cells' growth. However, the natural form of curcumin is prone to degrade and unstable in vitro. Here, we demonstrated that demethoxycurcumin (a curcumin-related demethoxy compound) could inhibit cell proliferation and induce apoptosis of ovarian cancer cells. Moreover, IRS2/ PI3K/Akt axis was inactivated in cells treated with demethoxycurcumin. Quantitative real-time reverse transcription polymerase chain reaction demonstrated that miR-551a was down-regulated in ovarian cancer tissues and ovarian cancer cell lines. Over-expression of miR-551a inhibited cell proliferation and induced apoptosis of ovarian cancer cells, whereas down-regulation of miR-551a exerted the opposite function. Luciferase assays confirmed that there was a binding site of miR-551a in IRS2, and we found that miR-551a exerted tumor-suppressive function by targeting IRS2 in ovarian cancer cells. Remarkably, miR-551a was up-regulated in the cells treated with demethoxycurcumin, and demethoxycurcumin suppressed IRS2 by restoration of miR-551a. In conclusion, demethoxycurcumin hindered ovarian cancer cells' malignant progress via up-regulating miR-551a.

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Section: Discussionmentioning

confidence: 98%

Demethoxycurcumin inhibited human epithelia ovarian cancer cells’ growth via up-regulating miR-551a

Sha²

2017

Tumour Biol.

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“…MicroRNA array showed that microRNA-195 chemosensitizes CC cells to the chemotherapeutic drug doxorubicin by targeting the first binding site of B-cell CLL/lymphoma 2-like protein 2 (bCL2L2) mRNA (29). Mussnich et al reported that miR-199a-5p and miR-375 affect CC cell sensitivity to cetuximab by targeting the PH domain and leucine rich repeat protein phosphatase 1 (PHLPP1) (30). MicroRNA-425-5p was also reported to reduce 5-FU resistance in colorectal cancer cells via the regulation of programmed cell death 10 (21).…”

Section: Mir-20b Reduces 5-fu Resistance In the Hct116-r Cellsmentioning

confidence: 99%

miR-20b reduces 5-FU resistance by suppressing the ADAM9/EGFR signaling pathway in colon cancer

Cheng

Zhang

et al. 2016

Oncology Reports

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Chemoresistance is a major obstacle to cancer therapy including that of colon cancer (CC). Although the dysregulation of many miRNAs has been implicated in 5-fluorouracil (5-FU) resistance in CC cells, the specific role of miR-20b in chemoresistance has not been documented. In the present study, we first determined the expression of miR-20b by RT-PCR and the levels of a disintegrin and metalloprotease 9 (ADAM9) and epidermal growth factor receptor (EGFR) by western blotting in CC and adjacent non-cancerous tissues from 5-FU-sensitive or -resistant CC patients. Subsequently, 5-FU-sensitive (HCT116) and -resistant (HCT116-R) cells were obtained, and the levels of miR-20b, ADAM9 and EGFR were detected. Meanwhile, the 5-FU resistance of the cells was examined by assessing cell viability (by MTT assay) and apoptosis (by flow cytometry). After transfection of miR-20b into HCT116-R cells, drug resistance was reexamined. We then confirmed the relationship between miR-20b and ADAM9 by luciferase reporter assay. Finally, 5-FU resistance in HCT116 and HCT116-R cells was compared after transfection with miR-20b. Our results showed that miR-20b was expressed at lower levels in the 5-FU-resistant tissues and cells than in the 5-FU-sensitive tissues and cells. The opposite was the case for expression of ADAM9 and EGFR. In addition, we demonstrated that ADAM9 is a direct target of miR-20b and that miR-20b decreased the 5-FU resistance of HCT116-R cells. Our findings suggest that miR-20b reduces 5-FU resistance to induce apoptosis in vitro by suppressing ADAM9/EGFR in CC cells.

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“…It is not clear how miR-22 mediates activation of PTEN only in muted but not wide-type p53 cells. Similarly, miR-199a-5p and miR-375 increase resistance to cetuximab in CRC partially due to their repression of a common target PHLPP1, a tumor suppressor that negatively regulates the AKT pathway (Mussnich et al, 2015). Studies have shown KRAS mutations are correlated with acquired resistance to anti-EGFR therapy in CRC (Misale et al, 2012).…”

Section: Apoptosismentioning

confidence: 99%

MicroRNAs are important regulators of drug resistance in colorectal cancer

Zhang

Wang

2017

Biological Chemistry

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Despite of continuous development of cancer treatment over the past decades, drug resistance is still one of the major hurdles of effective therapy for advanced colorectal cancer (CRC) worldwide and the understanding of its underlying mechanisms remains limited. Emerged data suggests that many microRNAs (miRNAs) may contribute to drug resistance in CRC. Major findings on miRNA functions in drug resistance of CRC are systemically reviewed here, with the goal of providing new updates to broaden our comprehension of its mechanisms and evidence to utilize miRNAs as potential therapeutic targets for CRC treatment.

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MiR-199a-5p and miR-375 affect colon cancer cell sensitivity to cetuximab by targeting PHLPP1

Abstract: This study proposes miR-199a-5p and miR-375 as contributors to CTX resistance in colon cancer and suggests a novel approach based on miRNAs as tools for the therapy of this tumor.

Cited by 61 publications

References 33 publications

Demethoxycurcumin inhibited human epithelia ovarian cancer cells’ growth via up-regulating miR-551a

Demethoxycurcumin inhibited human epithelia ovarian cancer cells’ growth via up-regulating miR-551a

miR-20b reduces 5-FU resistance by suppressing the ADAM9/EGFR signaling pathway in colon cancer

MicroRNAs are important regulators of drug resistance in colorectal cancer

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