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      Downregulation of Serum miR-133b and miR-206 Associate with Clinical Outcomes of Progression as Monitoring Biomarkers for Metastasis Colorectal Cancer Patients

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          Abstract

          Background

          Colorectal cancer (CRC) is the third most common cancer in the world. Non-coding RNAs or microRNAs (miRNAs; miRs) biomarkers can play a role in cancer carcinogenesis and progression. Specific KRAS and EGFR mutation are associated with CRC development playing a role in controlling the cellular process as epigenetic events. Circulating serum miRs can serve for early diagnosis, monitoring, and prognosis of CRC as biomarkers but it is still unclear, clinically.

          Objective

          To determine potential biomarkers of circulating serum miR-133b and miR-206 in CRC patients

          Methods

          Bioinformatic prediction of microRNA was screened followed by TargetScanHuman7.2, miRTar2GO, miRDB, MiRanda, and DIANA-microT-CDS. Forty-four CRC serum (19 locally advanced, 23 distant advanced CRC) and 12 normal serum samples were subsequently extracted for RNA isolation, cDNA synthesis, and miR validation. The candidate circulating serum miR-133b and miR-206 were validated resulting in a relative expression via quantitative RT-PCR. Relative expression was normalized to the spike-internal control and compared to normal samples as 1 using the -2ΔΔCt method in principle.

          Results

          Our results represented 9 miRs of miR-206, miR-155-5p, miR-143-3p, miR-193a-3p, miR-30a-5p, miR-30d-5p, miR-30e-5p, miR-543, miR-877-5p relate to KRAS-specific miRs, whereas, 9 miRs of miR-133b, miR-302a-3p, miR-302b-3p, miR-302d-3p, miR-302e, miR-520a-3p, miR-520b, miR-520c-3p and miR-7-5p relevance to EGFR-specific miRs by using the bioinformatic prediction tools. Our results showed a decreased expression level of circulating serum miR-133b as well as miR-206 associating with CRC patients (local and advanced metastasis) when compared to normal ( P < 0.05), significantly.

          Conclusion

          The circulating serum miR-133b and miR-206 can serve as significant biomarkers for monitoring the clinical outcome of progression with metastatic CRC patients. Increased drug-responsive CRC patients associated with crucial molecular intervention should be further explored, clinically.

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          Most cited references75

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          Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries

          This article provides an update on the global cancer burden using the GLOBOCAN 2020 estimates of cancer incidence and mortality produced by the International Agency for Research on Cancer. Worldwide, an estimated 19.3 million new cancer cases (18.1 million excluding nonmelanoma skin cancer) and almost 10.0 million cancer deaths (9.9 million excluding nonmelanoma skin cancer) occurred in 2020. Female breast cancer has surpassed lung cancer as the most commonly diagnosed cancer, with an estimated 2.3 million new cases (11.7%), followed by lung (11.4%), colorectal (10.0 %), prostate (7.3%), and stomach (5.6%) cancers. Lung cancer remained the leading cause of cancer death, with an estimated 1.8 million deaths (18%), followed by colorectal (9.4%), liver (8.3%), stomach (7.7%), and female breast (6.9%) cancers. Overall incidence was from 2-fold to 3-fold higher in transitioned versus transitioning countries for both sexes, whereas mortality varied <2-fold for men and little for women. Death rates for female breast and cervical cancers, however, were considerably higher in transitioning versus transitioned countries (15.0 vs 12.8 per 100,000 and 12.4 vs 5.2 per 100,000, respectively). The global cancer burden is expected to be 28.4 million cases in 2040, a 47% rise from 2020, with a larger increase in transitioning (64% to 95%) versus transitioned (32% to 56%) countries due to demographic changes, although this may be further exacerbated by increasing risk factors associated with globalization and a growing economy. Efforts to build a sustainable infrastructure for the dissemination of cancer prevention measures and provision of cancer care in transitioning countries is critical for global cancer control.
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            Characterization of microRNAs in serum: a novel class of biomarkers for diagnosis of cancer and other diseases.

            Dysregulated expression of microRNAs (miRNAs) in various tissues has been associated with a variety of diseases, including cancers. Here we demonstrate that miRNAs are present in the serum and plasma of humans and other animals such as mice, rats, bovine fetuses, calves, and horses. The levels of miRNAs in serum are stable, reproducible, and consistent among individuals of the same species. Employing Solexa, we sequenced all serum miRNAs of healthy Chinese subjects and found over 100 and 91 serum miRNAs in male and female subjects, respectively. We also identified specific expression patterns of serum miRNAs for lung cancer, colorectal cancer, and diabetes, providing evidence that serum miRNAs contain fingerprints for various diseases. Two non-small cell lung cancer-specific serum miRNAs obtained by Solexa were further validated in an independent trial of 75 healthy donors and 152 cancer patients, using quantitative reverse transcription polymerase chain reaction assays. Through these analyses, we conclude that serum miRNAs can serve as potential biomarkers for the detection of various cancers and other diseases.
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              Colorectal cancer statistics, 2023

              Colorectal cancer (CRC) is the second most common cause of cancer death in the United States. Every 3 years, the American Cancer Society provides an update of CRC statistics based on incidence from population-based cancer registries and mortality from the National Center for Health Statistics. In 2023, approximately 153,020 individuals will be diagnosed with CRC and 52,550 will die from the disease, including 19,550 cases and 3750 deaths in individuals younger than 50 years. The decline in CRC incidence slowed from 3%-4% annually during the 2000s to 1% annually during 2011-2019, driven partly by an increase in individuals younger than 55 years of 1%-2% annually since the mid-1990s. Consequently, the proportion of cases among those younger than 55 years increased from 11% in 1995 to 20% in 2019. Incidence since circa 2010 increased in those younger than 65 years for regional-stage disease by about 2%-3% annually and for distant-stage disease by 0.5%-3% annually, reversing the overall shift to earlier stage diagnosis that occurred during 1995 through 2005. For example, 60% of all new cases were advanced in 2019 versus 52% in the mid-2000s and 57% in 1995, before widespread screening. There is also a shift to left-sided tumors, with the proportion of rectal cancer increasing from 27% in 1995 to 31% in 2019. CRC mortality declined by 2% annually from 2011-2020 overall but increased by 0.5%-3% annually in individuals younger than 50 years and in Native Americans younger than 65 years. In summary, despite continued overall declines, CRC is rapidly shifting to diagnosis at a younger age, at a more advanced stage, and in the left colon/rectum. Progress against CRC could be accelerated by uncovering the etiology of rising incidence in generations born since 1950 and increasing access to high-quality screening and treatment among all populations, especially Native Americans.
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                Author and article information

                Journal
                MIRNA
                MicroRNA
                MicroRNA
                MicroRNA
                Bentham Science Publishers
                2211-5366
                2211-5374
                2024
                : 13
                : 1
                : 56-62
                Affiliations
                [1 ] deptCollege of Medicine and Public Health , Ubon Ratchathani University , Ubon Ratchathani, , 34190, , Thailand, ;
                [2 ] deptBiomedical Science Research Unit , Ubon Ratchathani University , Ubon Ratchathani, , 34190, , Thailand,
                Author notes
                [* ]Address correspondence to this author at the College of Medicine and Public Health, Ubon Ratchathani University, Ubon Ratchathani, 34190, Thailand; E-mail: Surasak.w@ 123456ubu.ac.th
                Article
                MIRNA-13-1-56
                10.2174/0122115366266024240101075745
                11503644-0ea3-4aad-a754-a9dd69a5b65c
                Copyright @ 2024

                © 2024 The Author(s). Published by Bentham Science Publisher. This is an open access article published under CC BY 4.0 https://creativecommons.org/licenses/by/4.0/legalcode

                History
                : 22 August 2023
                : 10 November 2023
                : 16 November 2023
                Categories
                Life Sciences, Genetics & Genomics, Biochemistry & Molecular Biology, Genetics & Heredity, Cell Biology

                Medicine,Chemistry,Life sciences
                circulating microRNAs,serum miR-206,miRNAs validation,Colorectal cancer,prognostic biomarkers,serum miR-133b

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