The Inhibitory Role of miR-486-5p on CSC Phenotype Has Diagnostic and Prognostic Potential in Colorectal Cancer

Pisano, Andrea; Griñán‐Lisón, Carmen; Farace, Cristiano; Fiorito, Giovanni; Fenu, Grazia; Jiménez, Gema; Scognamillo, Fabrizio; Peña-Martin, Jesùs; Naccarati, Alessio; Pröll, Johannes; Atzmüller, S.; Pardini, Barbara; Attene, Federico; Ibba, Gabriele; Solinas, Giuliana; Bernhard, David; Marchal, Juan A.; Madeddu, Roberto

doi:10.3390/cancers12113432

Cited by 19 publications

(9 citation statements)

References 93 publications

(127 reference statements)

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“…miR-486-5p also suppressed EMT in GC. These results indicated that miR-486-5p functioned as a tumor suppressive miRNA in GC, which was similar with the function of miR-486-5p observed in other malignancies, such as lung cancer, colorectal cancer and prostate cancer (39,40).…”

Section: Discussionsupporting

confidence: 82%

miR‑486‑5p suppresses gastric cancer cell growth and migration through downregulation of fibroblast growth factor 9

et al. 2021

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Non-coding RNAs serve essential roles in regulating mRNA and protein expression and dysregulation of non-coding RNAs participates in a variety of types of cancer. microRNAs (miRNAs/miRs), which are 21-24 nucleotides non-coding RNAs, have been shown to be important for the development of gastric cancer (GC). However, the role of miR-486-5p in GC remains to be elucidated. The present study found that miR-486-5p was downregulated in GC tissues. Comparing with gastric normal cells GES-1, GC cells, including MKN-45, AGS, HGC27 and MKN74, had reduced abundance of miR-486-5p transcript. CCK8 and colony formation assays demonstrated that GC cell growth and proliferation were enhanced by miR-486-5p inhibitors and were suppressed by miR-486-5p mimics. miR-486-5p also suppressed cell cycle process and migration and promoted apoptosis in GC cells, as verified by propidium iodide (PI) staining, Transwell assay and PI/Annexin V staining. miR-486-5p downregulated fibroblast growth factor 9 (FGF9) through combining to its 3'untranslated region. Overexpression of FGF9 accelerated the growth and proliferation of GC cells. The expression of miR-486-5p was negatively associated with FGF9 mRNA expression in GC samples. These results revealed that miR-486-5p was a tumor suppressor in GC. Downregulation of FGF9 contributed to the role of miR-486-5p in GC.

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Section: Discussionsupporting

confidence: 82%

miR‑486‑5p suppresses gastric cancer cell growth and migration through downregulation of fibroblast growth factor 9

et al. 2021

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“…The finding of hsa-miR-486-5p expression exclusively in long-term survival patients supports the hypothesis that tumor progression determines a progressive decline for this miRNA expression, as occurs in colorectal cancer [51]. While no data in the literature report an association between hsa-miR-3135b and cancer progression and/or survival, hsa-miR-6126 has been recently identified by Mazza et al in PDAC plasma with levels increasing with metastases, but not correlated with survival [41].…”

Section: Discussionsupporting

confidence: 72%

Serum miRNA Profiling for Early PDAC Diagnosis and Prognosis: A Retrospective Study

et al. 2021

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Background: Tumor stage predicts pancreatic cancer (PDAC) prognosis, but prolonged and short survivals have been described in patients with early-stage tumors. Circulating microRNA (miRNA) are an emerging class of suitable biomarkers for PDAC prognosis. Our aim was to identify whether serum miRNA signatures predict survival of early-stage PDAC. Methods: Serum RNA from archival 15 stage I-III PDAC patients and 4 controls was used for miRNAs expression profile (Agilent microarrays). PDAC patients with comparable age, gender, diabetes, jaundice and surgery were classified according to survival: less than 14 months (7/15 pts, group A) and more than 22 months (8/15 pts, group B). Bioinformatic data analysis was performed by two-class Significance Analysis of Microarray (SAM) algorithm. Binary logistic regression analyses considering PDAC diagnosis and outcome as dependent variables, and ROC analyses were also performed. Results: 2549 human miRNAs were screened out. At SAM, 76 differentially expressed miRNAs were found among controls and PDAC (FDR = 0.4%), the large majority (50/76, 66%) of them being downregulated in PDAC with respect to controls. Six miRNAs were independently correlated with early PDAC, and among these, hsa-miR-6821-5p was associated with the best ROC curve area in distinguishing controls from early PDAC. Among the 71 miRNAs differentially expressed between groups A and B, the most significant were hsa-miR-3135b expressed in group A only, hsa-miR-6126 and hsa-miR-486-5p expressed in group B only. Eight miRNAs were correlated with the presence of lymph-node metastases; among these, hsa-miR-4669 is of potential interest. hsa-miR-4516, increased in PDAC and found as an independent predictor of survival, has among its putative targets a series of gens involved in key pathways of cancer progression and dissemination, such as Wnt and p53 signalling pathways. Conclusions: A series of serum miRNAs was identified as potentially useful for the early diagnosis of PDAC, and for establishing a prognosis.

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“…As far as miRNA biomarkers are concerned, a striking example is the miR-486-5p, whose levels have been revealed to be downregulated in patients with metastatic CRC. According to novel genomic data, the potential inhibitory role of this emerging diagnostic biomarker could be attributed to the negative regulation of the expression of stemness-related transcription factors and the major pathways of CSCs: TGF-β, Notch, Hedgehog, and Wnt [ 32 ].…”

Section: Genetic Mutations In Crcmentioning

confidence: 99%

Resectable Colorectal Cancer: Current Perceptions on the Correlation of Recurrence Risk, Microbiota and Detection of Genetic Mutations in Liquid Biopsies

Koulouris

Tsagkaris

Messaritakis

et al. 2021

Cancers

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Metastatic colorectal cancer (mCRC) remains a highly lethal malignancy, although considerable progress has resulted from molecular alterations in guiding optimal use of available treatments. CRC recurrence remains a great barrier in the disease management. Hence, the spotlight turns to newly mapped fields concerning recurrence risk factors in patients with resectable CRC with a focus on genetic mutations, microbiota remodeling and liquid biopsies. There is an urgent need for novel biomarkers to address disease recurrence since specific genetic signatures can identify a higher or lower recurrence risk (RR) and, thus, be used both as biomarkers and treatment targets. To a large extent, CRC is mediated by the immune and inflammatory interplay of microbiota, through intestinal dysbiosis. Clarification of these mechanisms will yield new opportunities, leading not only to the appropriate stratification policies, but also to more precise, personalized monitoring and treatment navigation. Under this perspective, early detection of post-operative CRC recurrence is of utmost importance. Ongoing trials, focusing on circulating tumor cells (CTCs) and, even more, circulating tumor DNA (ctDNA), seem to pave the way to a promising, minimally invasive but accurate and life-saving monitoring, not only supporting personalized treatment but favoring patients’ quality of life, as well.

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The Inhibitory Role of miR-486-5p on CSC Phenotype Has Diagnostic and Prognostic Potential in Colorectal Cancer

Cited by 19 publications

References 93 publications

miR‑486‑5p suppresses gastric cancer cell growth and migration through downregulation of fibroblast growth factor 9

miR‑486‑5p suppresses gastric cancer cell growth and migration through downregulation of fibroblast growth factor 9

Serum miRNA Profiling for Early PDAC Diagnosis and Prognosis: A Retrospective Study

Resectable Colorectal Cancer: Current Perceptions on the Correlation of Recurrence Risk, Microbiota and Detection of Genetic Mutations in Liquid Biopsies

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