Oncogenic miRNAs and target therapies in colorectal cancer

Saberinia, Amin; Alinezhad, Amin; Jafari, Fatemeh; Soltany, Setareh; Sigari, Reza Akhavan

doi:10.1016/j.cca.2020.05.012

Cited by 32 publications

(18 citation statements)

References 209 publications

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“…Several DE c-miRs have been implicated to sporadic cancer progression (41,42). To study this in our dataset, we compared sporadic rectal cancer patients to non-LS controls.…”

Section: Resultsmentioning

confidence: 99%

Systemic circulating microRNA landscape in Lynch syndrome

Sievänen

Korhonen

Jokela

et al. 2022

Preprint

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MicroRNAs (miRs) are non-coding RNA-molecules that regulate gene expression. Global circulating miR (c-miR) expression patterns (c-miRnome) change with carcinogenesis in various sporadic cancers. Therefore, aberrantly expressed c-miRs could have diagnostic, predictive and prognostic potential in molecular profiling of cancers. c-miR functions in carriers of inherited pathogenic mismatch-repair gene variants (path_MMR), also known as Lynch syndrome (LS), have remained understudied. LS cohort provides an ideal population for biomarker mining due to increased lifelong cancer risk and excessive cancer occurrence. Using high-throughput sequencing and bioinformatic approaches, we conducted an exploratory analysis to characterize systemic c-miRnomes of path_MMR carriers. Our discovery cohort included 81 healthy path_MMR carriers and 37 non-LS controls. Our analysis also included cancer cohort comprised of 13 path_MMR carriers with varying cancers and 24 sporadic rectal cancer patients. We showed for the first time that c-miRnome can discern healthy path_MMR carriers from non-LS controls but does not distinguish healthy path_MMR carriers from cancer patients with or without path_MMR. Our c-miR expression analysis combined with in silico tools suggest ongoing alterations of biological pathways shared in LS and sporadic carcinogenesis. We observed that these alterations can produce a c-miR signature which can be used to track oncogenic stress in cancer-free path_MMR carriers. Thus, c-miRs hold potential in monitoring which cancer patients would require more intensive surveillance or clinical management.

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“…Several DE c-miRs have been implicated to sporadic cancer progression (41,42). To study this in our dataset, we compared sporadic rectal cancer patients to non-LS controls.…”

Section: Resultsmentioning

confidence: 99%

Systemic circulating microRNA landscape in Lynch syndrome

Sievänen

Korhonen

Jokela

et al. 2022

Preprint

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“…Immunohistochemistry (IHC) staining was carried out as our previously described (23). Brie y, formalinxed tissues were embedded in para n and cut into 4-μm-thick sections.…”

Section: Immunohistochemistry Stainingmentioning

confidence: 99%

“…MicroRNAs (miRNAs) are a type of highly conserved and endogenous noncoding RNA, with [17][18][19][20][21][22][23][24][25] nucleotides long in size, which can regulate various cellular processes, including cell proliferation, differentiation, apoptosis, migration and metastasis [5][6][7]. Growing evidences support that miRNAs have played crucial roles in progression of various cancers [6,8].…”

Section: Introductionmentioning

confidence: 99%

MiR-128-1-5p inhibits cell proliferation and induces cell apoptosis via targeting PRKCQ in colorectal cancer

Jia

Liao

et al. 2022

Preprint

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Background MicroRNAs (miRNAs) are a type of highly conserved and endogenous noncoding RNA which can regulate various cellular processes, including cell proliferation, differentiation, apoptosis, migration and metastasis. Aberrant expression of miR-128-5p, has been shown to be a key regulator in tumorigenesis and cancer development. But the role and the underlying molecular mechanisms of miR-128 in CRC still remain largely unknown. Methods The expression and clinical significances of miR-128-1-5p in colorectal cancer tissues and cell lines was quantified by qRT-PCR. Stably transfected cell lines were established by infecting SW620 and LOVO cells with lentiviruses. The functions of miR-128-1-5p were measured by CCK-8 assay, Annexin V- DY-634 PI Apoptosis Staining / Detection, and Xenograft model. Western blotting, immunohistochemistry (IHC), luciferase reporter assays and Bioinformatic Analysis were also used in this study. Results MiR-128-1-5p was downregulated in CRC and was associated with optimal survival in CRC. Overexpression of miR-128-1-5p inhibited cell proliferation and induced cell apoptosis. Protein tyrosine kinase C theta isoform (PRKCQ) was a direct target of miR-128-1-5p and was involved in miR-128-1-5p-mediated proliferation and apoptosis. Conclusions These results provide novel insight into the role of miR-128-1-5p in CRC. Overexpression of miR-128-1-5p was associated with cell proliferation and apoptosis in CRC. Knockdown of miR-128-1-5p reduced CRC growth by modulating PRKCQ expression and is a possible new therapeutic target for patients with CRC.

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“…Studies have revealed that numerous miRNAs (including miR-21, miR-17-92 cluster, miR-143 and miR-145) are deregulated in patients with CRC and serve an important role in its initiation, development, and progression (20)(21)(22). One of the most commonly upregulated miRNAs in CRC is miR-21, which plays an essential role in tumor progression (23).…”

Section: Introductionmentioning

confidence: 99%

Study of microRNA expression profiling as biomarkers for colorectal cancer patients in Lebanon

Staiteieh

Akil²,

Khansa

et al. 2021

Mol Clin Oncol

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The high incidence and mortality rates of colorectal cancer (CRC) reveal its hazardous effect globally. Thus, it is important to diagnose CRC at an early stage to decrease its burden and improve survival rates. Previous studies have investigated the role of short non-coding microRNAs (miRNAs or miRs) in numerous types of cancer, including CRC. Previous studies have been performed to investigate the role of miRNAs as biomarkers in diagnosis, prognosis and prediction of CRC development. The aim of the present retrospective study was to identify the expression levels of miR-31, miR-145, miR-146b and miR-186 to highlight their role in CRC diagnosis and progression at different stages of the disease (precancerous polyp, adenoma and adenocarcinoma) in a Lebanese population. The expression levels of miRNAs was revealed using TaqMan reverse transcription-quantitative PCR on formalin-fixed paraffin-embedded tissues from Lebanese patients at different stages; their diagnostic value was determined using a receiver operating characteristics curve. Compared with healthy controls, miR-31 was upregulated (P<0.0001) at all stages. By contrast, miR-145, miR-186, and miR-146b were significantly downregulated at all stages (P<0.0001, P=0.0009 and P=0.0241, respectively). Of the four miRNAs studied, miR-31 and miR-145 were identified as potentially useful diagnostic factors, with an area under the curve of 0.7771 and 0.8269 and diagnostic accuracy of 71.3 and 78.5%, respectively. These data suggested that miR-31 and miR-145, upon further clinical validation, may be used as potential diagnostic biomarkers for the early detection of CRC at the polyp stage.

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Oncogenic miRNAs and target therapies in colorectal cancer

Cited by 32 publications

References 209 publications

Systemic circulating microRNA landscape in Lynch syndrome

Systemic circulating microRNA landscape in Lynch syndrome

MiR-128-1-5p inhibits cell proliferation and induces cell apoptosis via targeting PRKCQ in colorectal cancer

Study of microRNA expression profiling as biomarkers for colorectal cancer patients in Lebanon

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