Upregulated miR-16 expression is an independent indicator of relapse and poor overall survival of colorectal adenocarcinoma patients

Diamantopoulos, Marios A.; Kontos, Christos K.; Kerimis, Dimitrios; Papadopoulos, Iordanis N.; Scorilas, Andreas

doi:10.1515/cclm-2016-0756

Cited by 33 publications

(21 citation statements)

References 43 publications

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“…In contrast, miR-16 was upregulated in CT and S, particularly in the LOW grade and no-Met patients, suggesting that high level of miR-16 in cancer tissues is an early diagnostic marker of CRC. This is consistent with several studies that have reported high levels of miR-16 in CRC tissues [60] and/or its association with overall survival [61,62], but in contrast to other studies that have reported its downregulation in CRC [63]. Because this miRNA was downregulated in all CSC types, its reduced expression in patients with CRC could be a marker of poor prognosis.…”

Section: Discussionsupporting

confidence: 92%

Deregulation of cancer-stem-cell-associated miRNAs in tissues and sera of colorectal cancer patients

et al. 2020

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Copyright: Farace et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License 3.0 (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. ABSTRACTColorectal cancer (CRC) is a deadly tumour in Western countries characterized by high cellular/molecular heterogeneity. Cancer stem cells (CSC) act in cancer recurrence, drug-resistance and in metastatic epithelial-to-mesenchymal transition. microRNAs (miRNAs) contribute to cancer is increasing, and miRNA roles in CSC phenotype and fate and their utility as CRC biomarkers have also been reported. Here, we investigated miR-21, miR-221, miR-18a, miR-210, miR-31, miR-34a, miR-10b and miR-16 expression in experimental ALDH + and CD44 + /CD326 + colorectal CSCs obtained from the human CRC cell lines HCT-116, HT-29 and T-84. Then, we moved our analysis in cancer tissue (CT), healthy tissue (HT) and serum (S) of adult CRC patients (n=12), determining relationships with clinical parameters (age, sex, metastasis, biochemical serum markers). Specific miRNA patterns were evident in vitro (normal, monolayers and CSCs) and in patients' samples stratified by TNM stage (LOW vs HIGH) or metastasis (Met vs no-Met). miR-21, miR-210, miR-34a upregulation ad miR-16 dowregulation associated with the CSCs phenotype. miR-31b robustly overexpressed in monolayers and CSCs, and in CT ad S of HIGH grade and Met patients, suggesting a role as marker of CRC progression and metastasis. miR-18a upregulated in all cancer models and associated to CSC phenotype, and to metastasis and age in patients. miR-10b downregulated in CT and S of LOW/HIGH grade and no-Met patients. Our results identify miRNAs useful as colorectal CSC biomarker and that miR-21, miR-210, miR-10b and miR-31b are promising markers of CRC. A specific role of miR-18a as metastatic CRC serum biomarker in adult patients was also highlighted. www.oncotarget.com

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Section: Discussionsupporting

confidence: 92%

Deregulation of cancer-stem-cell-associated miRNAs in tissues and sera of colorectal cancer patients

et al. 2020

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“…Among the evaluated studies, 49 demonstrated the downregulation of miR-199b 47, 48 , miR-6852 106 , miR-302c 67 , miR-466 68 , miR-650 123 , miR-196b-5p 70 , miR-944 71 , miR-30d 72 , miR-296 73 , miR-187 124 , let-7a-5p 98 , miR-132 99 , miR-206 100 , miR-148a 125 , miR-33b 76 , miR-99b-5p 120 , miR-154 78 , miR-217 126 , miR-149 79 , miR-194 80 , miR-7 56 , miR-24-3p 54 , miR-29b 127 , miR-15a 34 , miR-16 34, 36 , miR-204-5p 128 , miR-96-5p 121 , miR-193a-5p 108 , miR-100 81 , miR-133a 41 , miR-139-5p 129 , miR-124-5p 130 , miR-335 82 , miR-378 101 , miR-126 40 , miR-378a-3p 58 , miR-378a-5p 58 , miR-218 83 , miR-138 110 , miR-625 111 , miR-212 112 , miR-124 131 , miR-22 49 , miR-133b 39 , miR-193a-3p 104 , miR-195 113 and miR-30c 103 associated with worse prognosis (lower overall survival) of CRC patients. Fifty-six studies identified the upregulation of miR-181a 31–33 , miR-182 43, 44 , miR-1296 84 , miR-888 64 , miR-28-5p 132 , miR-183 45, 46 , miR-200c 114 , miR-34a 133 , miR-15a-5p 134 , miR-181c 135 , miR-24-3p 53 , miR-16 35 , miR-7 55 , miR-96 86 , miR-1260b 115 , miR-20a-5p 63 , miR-517a 87 , miR-503 136 , miR-106b 88 , miR-211 137 , miR-320e 89 , miR-592 90 , miR-196a 57 , miR-196b 57 , miR-376a …”

Section: Resultsmentioning

confidence: 99%

“…In total, 17 studies demonstrated the downregulation of 18 miRs associated with worse disease free-survival such as miR-196b-5p 70 , miR-944 71 , miR-30d 72 , miR-22 50 , miR-296 73 , miR-199b 47 , miR-187 124 , let-7a-5p 98 , miR-132 99 , miR-29b 127 , miR-15a 34 , miR-16 34 , miR-34a-5p 65 , miR-193a-5p 108 , miR-138 110 , miR-126 8 , miR-212 112 and miR-124 131 . Twenty-one studies associated the upregulation of miR-888 64 , miR-28-5p 132 , miR-183 45 , miR-200c 114 , miR-34a 133 , miR-15a-5p 134 , miR-181c 135 , miR-24-3p 53 , miR-16 35 , miR-96 86 , miR-1260b 115 , miR-20a-5p 63 , miR-517a 87 , miR-503 136 , miR-106b 88 , miR-320e 89 , miR-196a 57 , miR-196b 57 , miR-224 51 , miR-494 61 , miR-181a 32 , miR-21 25, 26, 30 and miR-155 30 with worse disease free-survival.…”

Section: Resultsmentioning

confidence: 99%

Tissue micro-RNAs associated with colorectal cancer prognosis: a systematic review

Santos

Penna

Carneiro

et al. 2019

Preprint

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Colorectal cancer (CRC) is a multifactorial disease commonly diagnosed worldwide, with high mortality rates. Several studies demonstrate important associations between differential expression of micro-RNAs (miRs) and the prognosis of CRC. However, only a few systematic reviews emphasize the most relevant miRs able to contribute to the establishment of new prognostic biomarkers in CRC patients. The present study aimed to identify differentially expressed tissue miRs associated with prognostic factors in CRC patients, through a systematic review of the Literature. Using the PubMed database, Cochrane Library and Web of Science, studies published in English evaluating miRs differentially expressed in tumor tissue and significantly associated with the prognostic aspects of CRC were selected. All the included studies used RT-PCR (Taqman or SYBR Green) for miR expression analysis and the period of publication was from 2009 to 2018. A total of 115 articles accomplished the inclusion criteria and were included in the review. The studies investigated the expression of 102 different miRs associated with prognostic aspects in colorectal cancer patients. The most frequent oncogenic miRs investigated were miR-21, miR-181a, miR-182, miR-183, miR-210 and miR-224 and the hyperexpression of these miRs was associated with distant metastasis, lymph node metastasis and worse survival in patients with CRC. The most frequent tumor suppressor miRs were miR-126, miR-199b and miR-22 and the hypoexpression of these miRs was associated with distant metastasis, worse prognosis and a higher risk of disease relapse (worse disease-free survival). Specific tissue miRs are shown to be promising prognostic biomarkers in patients with CRC, given their strong association with the prognostic aspects of these tumors, however, new studies are necessary to establish the sensibility and specificity of the miRs in order to use them in clinical practice.

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“…Among these it can be distinguished that the levels of 37 C-miRNAs have been found to be up-regulated (Table 4) while the levels of nine miRNAs were found to be down-regulated (Table 4). Another group of two C-miRNAs were found to be disregulated (Table 4), and can be used in the future to define a signature of tumor presence and stage [156].…”

Section: Gastrointestinal Oncologymentioning

confidence: 99%

The circulating miRNAs as diagnostic and prognostic markers

Terrinoni

Calabrese

Basso

et al. 2018

Clinical Chemistry and Laboratory Medicine (CCLM)

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A large portion of the human genome transcribes RNA sequences that do not code for any proteins. The first of these sequences was identified in 1993, and the best known noncoding RNAs are microRNA (miRNAs). It is now fully established that miRNAs regulate approximately 30% of the known genes that codify proteins. miR-NAs are involved in several biological processes, like cell proliferation, differentiation, apoptosis and metastatization. These RNA products regulate gene expression at the post-transcriptional level, modulating or inhibiting protein expression by interacting with specific sequences of mRNAs. Mature miRNAs can be detected in blood plasma, serum and also in a wide variety of biological fluids. They can be found associated with proteins, lipids as well as enclosed in exosome vesicles. We know that circulating miRNAs (C-miRNAs) can regulate several key cellular processes in tissues different from the production site. C-miRNAs behave as endogenous mediators of RNA translation, and an extraordinary knowledge on their function has been obtained in the last years. They can be secreted in different tissue cells and associated with specific pathological conditions. Significant evidence indicates that the initiation and progression of several pathologies are "highlighted" by the presence of specific C-miRNAs, underlining their potential diagnostic relevance as clinical biomarkers. Here we review the current literature on the possible use of this new class of molecules as clinical biomarkers of diseases.

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Upregulated miR-16 expression is an independent indicator of relapse and poor overall survival of colorectal adenocarcinoma patients

Abstract: Overexpression of the cancer-associated miR-16 predicts poor DFS and OS of colorectal adenocarcinoma patients, independently of clinicopathological factors that are currently used for prognostic purposes.

Cited by 33 publications

References 43 publications

Deregulation of cancer-stem-cell-associated miRNAs in tissues and sera of colorectal cancer patients

Deregulation of cancer-stem-cell-associated miRNAs in tissues and sera of colorectal cancer patients

Tissue micro-RNAs associated with colorectal cancer prognosis: a systematic review

The circulating miRNAs as diagnostic and prognostic markers

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