Tumor suppressor miR‐193a‐3p enhances efficacy of BRAF/MEK inhibitors in BRAF‐mutated colorectal cancer

Hiraide, Sakura; Takahashi, Masanobu; Yoshida, Yuya; Yamada, Hideharu; Komine, Keigo; Ishioka, Chikashi

doi:10.1111/cas.15075

Cited by 9 publications

(8 citation statements)

References 50 publications

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“…Moreover, miR-143 and miR-145 have been well established to exert tumor-suppressive effects and are beneficial for the efficacy of anti-EGFR treatment in CRC, whereas miR-31-3p comes to the opposite. It has been shown that the overexpression of miR-193a-3p can promote BRAF -mutant CRC cells apoptosis by inhibiting the expression of KRAS and myeloid cell leukemia-1 (Mcl1) through MAPK signal ( 47 ). As a tumor suppressor, miR-193a-3p promotes the efficacy of BRAF inhibitor dabrafenib (DAB) and MEK inhibitor trametinib (TRA), and enhances the anti-proliferative effect of combined therapy of DAB, TRA with cetuximab in CRC ( 47 ).…”

Section: Mirnasmentioning

confidence: 99%

“…Synthetic miR-143 (miR-143#12) inhibits KRAS signaling pathway activation and restores the sensitivity of cetuximabresistant CRC cells by targeting the KRAS activating protein SOS1 (43). Overexpression of miR-143 or miR-145 can increase the sensitivity to cetuximab by enhancing cetuximab-mediated antibody-dependent cellular cytotoxicity (ADCC) in CRC cells (44) (47). As a tumor suppressor, miR-193a-3p promotes the efficacy of BRAF inhibitor dabrafenib (DAB) and MEK inhibitor trametinib (TRA), and enhances the antiproliferative effect of combined therapy of DAB, TRA with cetuximab in CRC (47).…”

Section: Impact Of Mirnas On Ras Signaling Pathwaymentioning

confidence: 99%

“…Overexpression of miR-143 or miR-145 can increase the sensitivity to cetuximab by enhancing cetuximab-mediated antibody-dependent cellular cytotoxicity (ADCC) in CRC cells (44) (47). As a tumor suppressor, miR-193a-3p promotes the efficacy of BRAF inhibitor dabrafenib (DAB) and MEK inhibitor trametinib (TRA), and enhances the antiproliferative effect of combined therapy of DAB, TRA with cetuximab in CRC (47). A recent study has shown that 4-acetylantroquinonol B (4-AAQB) inhibits CRC cell proliferation and induces cell apoptosis by up-regulating miR-193a-3p, downregulating KRAS and inhibiting the activation of KRAS signaling pathway.…”

Section: Impact Of Mirnas On Ras Signaling Pathwaymentioning

confidence: 99%

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Non-Coding RNAs Regulate the Resistance to Anti-EGFR Therapy in Colorectal Cancer

et al. 2022

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Colorectal cancer (CRC) is the third prevalent cancer worldwide, the morbidity and mortality of which have been increasing in recent years. As molecular targeting agents, anti-epidermal growth factor receptor (EGFR) monoclonal antibodies (McAbs) have significantly increased the progression-free survival (PFS) and overall survival (OS) of metastatic CRC (mCRC) patients. Nevertheless, most patients are eventually resistant to anti-EGFR McAbs. With the intensive study of the mechanism of anti-EGFR drug resistance, a variety of biomarkers and pathways have been found to participate in CRC resistance to anti-EGFR therapy. More and more studies have implicated non-coding RNAs (ncRNAs) primarily including microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs), are widely involved in tumorigenesis and tumor progression. They function as essential regulators controlling the expression and function of oncogenes. Increasing data have shown ncRNAs affect the resistance of molecular targeted drugs in CRC including anti-EGFR McAbs. In this paper, we have reviewed the advance in mechanisms of ncRNAs in regulating anti-EGFR McAbs therapy resistance in CRC. It provides insight into exploring ncRNAs as new molecular targets and prognostic markers for CRC.

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Section: Mirnasmentioning

confidence: 99%

Section: Impact Of Mirnas On Ras Signaling Pathwaymentioning

confidence: 99%

Section: Impact Of Mirnas On Ras Signaling Pathwaymentioning

confidence: 99%

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Non-Coding RNAs Regulate the Resistance to Anti-EGFR Therapy in Colorectal Cancer

et al. 2022

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“…MicroRNAs (miRNAs), containing 22 to 25 nucleotides, belong to single-stranded ribonucleic acid and exert function by degrading or inhibiting the translation of other proteins to regulate gene expression [ 7 ]. Dysregulation of miRNAs were closely associated with the occurrence of various diseases, especially cancers [ 8 – 12 ]. In lung cancer, miRNA-569 can be used as a tumor suppressor to induce apoptosis [ 13 ].…”

Section: Introductionmentioning

confidence: 99%

microRNA-569 inhibits tumor metastasis in pancreatic cancer by directly targeting NUSAP1

Che

et al. 2022

Aging

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MicroRNAs (miRNAs) are known to be involved in the development and progression of pancreatic cancer (PC). In this study, the prognostic significance and mechanistic role of microRNA-569 in PC were explored. Quantitative real-time PCR was used to detect the expression of microRNA-569 in PC tissues and cell lines. Scratch test and Transwell assay were conducted to detect migration and invasion ability. The xenograft nude mice model was used to determine tumor metastasis in vivo . The direct targets of microRNA-569 were determined by using bioinformatics analysis and a dual-luciferase reporter assay. The expression level of microRNA-569 was down-regulated in PC patients with a poor prognosis. In vitro and in vivo experiments indicated that over-expression of microRNA-569 inhibited the migration and invasion of PC cells. MicroRNA-569 negatively regulated NUSAP1 by directly binding its 3'-untranslated region. Further mechanism research implied that the ZEB1 pathway was involved in microRNA-569/NUSAP1 mediation of the biological behaviors in PC. These data demonstrated that microRNA-569 may exert a tumor-suppressing effect in PC and maybe a potential therapeutic target for PC patients.

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“…In addition, specific BRAF inhibitors are currently available. Oncogenic BRAF mutations occur in various malignancies, including malignant melanoma (50%), thyroid cancer (30%–50%), and colorectal cancer (10%) [ 6 ]. However, only a few cases of STS with BRAF mutation have been described [ 7 ].…”

Section: Introductionmentioning

confidence: 99%

BRAF and MEK Inhibitor Treatment for Metastatic Undifferentiated Sarcoma of the Spermatic Cord with BRAF V600E Mutation

Saijo¹,

Imai²,

Katayama³

et al. 2022

Case Rep Oncol

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An 18-year-old Japanese man was diagnosed with an undifferentiated sarcoma of the spermatic cord, with multiple distant metastases to the lungs and bones. The patient received doxorubicin-based standard chemotherapy. Although the chemotherapy was effective, it induced severe adverse events, which led to treatment discontinuation. A comprehensive genomic profiling test using resected tumor tissue revealed the BRAF V600E mutation. Based on the result, the patient received combination therapy with dabrafenib and trametinib. The combination therapy achieved a good response with few adverse events. However, 6.5 months later, pleural metastases and meningeal dissemination had emerged. A liquid comprehensive genomic profiling test was performed after the progression to identify the resistance mechanism, which resulted in the detection of no actionable gene alterations other than BRAF V600E. This report shows that the BRAF V600E mutation may be a promising therapeutic target and that resistance to the targeted therapy could also occur in soft tissue sarcoma. The significance of BRAF mutations across different types of cancer should be validated, and it is necessary to apply targeted therapies and develop methods to overcome resistance based on the optimal use of comprehensive genomic profiling tests.

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Tumor suppressor miR‐193a‐3p enhances efficacy of BRAF/MEK inhibitors in BRAF‐mutated colorectal cancer

Cited by 9 publications

References 50 publications

Non-Coding RNAs Regulate the Resistance to Anti-EGFR Therapy in Colorectal Cancer

Non-Coding RNAs Regulate the Resistance to Anti-EGFR Therapy in Colorectal Cancer

microRNA-569 inhibits tumor metastasis in pancreatic cancer by directly targeting NUSAP1

BRAF and MEK Inhibitor Treatment for Metastatic Undifferentiated Sarcoma of the Spermatic Cord with BRAF V600E Mutation

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