Identification of high‐risk Dukes B colorectal cancer by micro<scp>RNA</scp> expression profiling: a preliminary study

Aslam, Muhammad Imran; Venkatesh, J.; Jameson, J. S.; West, Kevin

doi:10.1111/codi.12886

Cited by 6 publications

(3 citation statements)

References 41 publications

(47 reference statements)

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“…However, the exact roles of miR-15b in CRC remain elusive. Our results are compatible with the report by Aslam et al (2015), which stated that expression of miR-15b was significantly downregulated in “high-risk B” tumors compared with Dukes A, “low-risk B” or C without metastasis in CRC. However, different groups reported that miR-15b could promote epithelial-mesenchymal transition (EMT) and tumor metastasis in pancreatic cancer, as well as inhibit apoptosis and correlate with poor prognosis in malignant melanoma (Satzger et al., 2010, Zhang et al., 2015), reflecting the complexity of regulation and functions of miRs in the context of different tumors.…”

Section: Discussionsupporting

confidence: 93%

Enhancement of Sensitivity to Chemo/Radiation Therapy by Using miR-15b against DCLK1 in Colorectal Cancer

Zhan

et al. 2018

Stem Cell Reports

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SummaryChemo-/radiotherapy resistance is the main cause accounting for most treatment failure in colorectal cancer (CRC). Tumor-initiating cells (TICs) are the culprit leading to CRC chemo-/radiotherapy resistance. The underlying regulation mechanism of TICs in CRC remains unclear. Here we discovered that miR-15b expression positively correlated with therapeutic outcome in CRC. Expression of miR-15b in pretreatment biopsy tissue samples predicted tumor regression grade (TRG) in rectal cancer patients after receiving neoadjuvant radiotherapy (nRT). Expression of miR-15b in post-nRT tissue samples was associated with therapeutic outcome. DCLK1 was identified as the direct target gene for miR-15b and its suppression was associated with self-renewal and tumorigenic properties of DCLK1+ TICs. We identified B lymphoma Mo-MLV insertion region l homolog (BMI1) as a downstream target regulated by miR-15b/DCLK1 signaling. Thus, miR-15b may serve as a valuable marker for prognosis and therapeutic outcome prediction. DCLK1 could be a potential therapeutic target to overcome chemo-/radioresistance in CRC.

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Section: Discussionsupporting

confidence: 93%

Enhancement of Sensitivity to Chemo/Radiation Therapy by Using miR-15b against DCLK1 in Colorectal Cancer

Zhan

et al. 2018

Stem Cell Reports

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“…7,8 New research showed that mi RNA is closely related to the development of tumors and plays an important role in the malignant characteristics of tumors. 9,10 At present, various miRNAs such as miR-25, miR-98, miR-34a, miR-194, mi R-495 and miR-365 have been confirmed to be involved in proliferation, differentiation, apoptosis and drug resistance of breast cancer cells. [11][12][13] Therefore, based on the regulation of miRNAs, further research on breast cancer-related miRNA and its mechanism of action can provide new ideas and directions for targeted therapy.…”

Section: Introductionmentioning

confidence: 99%

<p>MicroRNA-423 Drug Resistance and Proliferation of Breast Cancer Cells by Targeting ZFP36</p>

Xia¹,

Liu²,

Du³

et al. 2020

OTT

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Background/Aims: The effects of microRNA-423 on proliferation and drug resistance of breast cancer cells were explored, the downstream target genes of miR-423 and the targeted regulatory relationship between them were studied. Methods: RT-qPCR was used to detect the expression of miR-423 in breast cancer tissues and cell lines, and the transfection efficiency of miR-423 inhibitory vector miR-423-inhibitor was constructed and verified. CCK-8 and colony formation assays were used to examine the effect of miR-423 on tumor cell proliferation. Target gene prediction and screening and luciferase reporter assay were used to verify downstream target genes of miR-432. The mRNA and protein expression of miR-423target gene ZFP36 was detected by RT-qPCR and Western blotting. Results: The expression of miR-423 was significantly higher than that in normal tissues. Compared to the non-malignant mammary epithelial cell line MCF-10A, the expression of miR-423 was significantly raised in MCR-7 and MCF-7/ADR cells. ZFP36 was a downstream target gene of miR-423 and negatively correlated with the expression of miR-423 in breast cancer. The knockdown of miR-423 can significantly enhance the cytotoxicity of the drug, increase the apoptotic rate of MCF-7/ADR cells. miR-423 was capable of activating the Wnt/β-catenin signaling pathway leading to chemoresistance and proliferation, whereas overexpression of ZFP36 reduced drug resistance and proliferation. Conclusion: miR-423 acted as an oncogene to promote tumor cell proliferation and migration. ZFP36 was a downstream target gene of miR-423, and miR-423 inhibited the expression of ZFP36 via Wnt/β-catenin signaling pathway of breast cancer cells.

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“…Similarly, previous studies have also found an association between higher expression levels of FER1L4 and tumor suppressor functions [ 57 ], and between up-regulation of the miR-135b and BST2 genes and both metastatic [ 58 ] and poor prognosis colorectal tumors [ 59 ]. In this regard, Gaedcke et al [ 60 ] and Aslam et al [ 61 ] have previously reported an association between down-regulation of miR-135b in Dukes’ stage B sCRC patients who developed metastatic disease and a shorter disease-free survival; although these results are fully in line with our observations, they could not be systematically confirmed by others [ 58 , 59 ]. In turn, the greater BST2 gene expression levels found here among non-MTX tumors, could potentially be more related to the immunomodulatory role of stromal cells expressing BST2 in non-MTX sCRC, rather than the tumor cell-specific expression levels per se ; this would contribute to explain, at least in part, the apparent discrepant findings in the literature [ 62 ].…”

Section: Discussioncontrasting

confidence: 70%

Prognostic impact of a novel gene expression profile classifier for the discrimination between metastatic and non-metastatic primary colorectal cancer tumors

et al. 2017

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Despite significant advances have been achieved in the genetic characterization of sporadic colorectal cancer (sCRC), the precise genetic events leading to the development of distant metastasis remain poorly understood. Thus, accurate prediction of metastatic disease in newly-diagnosed sCRC patients remains a challenge. Here, we evaluated the specific genes and molecular pathways associated with the invasive potential of colorectal tumor cells, through the assessment of the gene expression profile (GEP) of coding and non-coding genes in metastatic (MTX) vs. non-metastatic (non-MTX) primary sCRC tumors followed for >5 years. Overall, MTX tumors showed up-regulation of genes associated with tumor progression and metastatic potential while non-MTX cases displayed GEP associated with higher cell proliferation, activation of DNA repair and anti-tumoral immune/inflammatory responses. Based on only 19 genes a specific GEP that classifies sCRC tumors into two MTX-like and non-MTX-like molecular subgroups was defined which shows an independent prognostic impact on patient overall survival, particularly when it is combined with the lymph node status at diagnosis. In summary, we show an association between the global GEP of primary sCRC cells and their metastatic potential and defined a GEP-based classifier that provides the basis for further prognostic stratification of sCRC patients who are at risk of distant metastases.

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Identification of high‐risk Dukes B colorectal cancer by microRNA expression profiling: a preliminary study

Abstract: The study suggests that the development of metastasis in Dukes B tumours may be predictable based on the miRNA expression of miR-15b and miR-135b. This requires further study on a much larger cohort.

Cited by 6 publications

References 41 publications

Enhancement of Sensitivity to Chemo/Radiation Therapy by Using miR-15b against DCLK1 in Colorectal Cancer

Enhancement of Sensitivity to Chemo/Radiation Therapy by Using miR-15b against DCLK1 in Colorectal Cancer

<p>MicroRNA-423 Drug Resistance and Proliferation of Breast Cancer Cells by Targeting ZFP36</p>

Prognostic impact of a novel gene expression profile classifier for the discrimination between metastatic and non-metastatic primary colorectal cancer tumors

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