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      MiR‐145 inhibits human colorectal cancer cell migration and invasion via PAK4‐dependent pathway

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          Abstract

          MicroRNA‐145 (miR‐145), as a tumor‐suppressive miRNA, has been demonstrated down‐regulated in colorectal cancer (CRC) cells, and could inhibit CRC cells growth. However, the molecular pathway in which miR‐145 modulates CRC malignant transformation has not been fully revealed. Here, we reported an intense correlation between the expressions of PAK4 and miR‐145 in human CRC cell lines. Transwell assay verified overexpression of miR‐145, as well as knockdown of PAK4, significantly suppressed cell migration and invasion ability. The impaired migration and invasion ability of SW1116 cells was affected through the down‐regulation of phosphorylation level of LIMK1 and cofilin in a PAK4‐dependent manner. Collectively, we have demonstrated that miR‐145 suppressed CRC migration and invasion through PAK4 pathway, which provides an attractive microRNA‐based therapeutic target for CRC.

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          Most cited references25

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          Cancer statistics, 2006.

          Each year, the American Cancer Society estimates the number of new cancer cases and deaths expected in the United States in the current year and compiles the most recent data on cancer incidence, mortality, and survival based on incidence data from the National Cancer Institute and mortality data from the National Center for Health Statistics. Incidence and death rates are age-standardized to the 2000 US standard million population. A total of 1,399,790 new cancer cases and 564,830 deaths from cancer are expected in the United States in 2006. When deaths are aggregated by age, cancer has surpassed heart disease as the leading cause of death for those younger than age 85 since 1999. Delay-adjusted cancer incidence rates stabilized in men from 1995 through 2002, but continued to increase by 0.3% per year from 1987 through 2002 in women. Between 2002 and 2003, the actual number of recorded cancer deaths decreased by 778 in men, but increased by 409 in women, resulting in a net decrease of 369, the first decrease in the total number of cancer deaths since national mortality record keeping was instituted in 1930. The death rate from all cancers combined has decreased by 1.5% per year since 1993 among men and by 0.8% per year since 1992 among women. The mortality rate has also continued to decrease for the three most common cancer sites in men (lung and bronchus, colon and rectum, and prostate) and for breast and colon and rectum cancers in women. Lung cancer mortality among women continues to increase slightly. In analyses by race and ethnicity, African American men and women have 40% and 18% higher death rates from all cancers combined than White men and women, respectively. Cancer incidence and death rates are lower in other racial and ethnic groups than in Whites and African Americans for all sites combined and for the four major cancer sites. However, these groups generally have higher rates for stomach, liver, and cervical cancers than Whites. Furthermore, minority populations are more likely to be diagnosed with advanced stage disease than are Whites. Progress in reducing the burden of suffering and death from cancer can be accelerated by applying existing cancer control knowledge across all segments of the population.
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            Reduced accumulation of specific microRNAs in colorectal neoplasia.

            Short non-coding RNAs are known to regulate cellular processes including development, heterochromatin formation, and genomic stability in eukaryotes. Given the impact of these processes on cellular identity, a study was undertaken to investigate possible changes in microRNA (miRNA) levels during tumorigenesis. A total of 28 different miRNA sequences was identified in a colonic adenocarcinoma and normal mucosa, including 3 novel sequences and a further 7 that had previously been cloned only from mice. Human homologues of murine miRNA sequences, miR-143 and miR-145, consistently display reduced steady-state levels of the mature miRNA at the adenomatous and cancer stages of colorectal neoplasia.
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              Worldwide variations in colorectal cancer.

              Previous studies have documented significant international variations in colorectal cancer rates. However, these studies were limited because they were based on old data or examined only incidence or mortality data. In this article, the colorectal cancer burden and patterns worldwide are described using the most recently updated cancer incidence and mortality data available from the International Agency for Research on Cancer (IARC). The authors provide 5-year (1998-2002), age-standardized colorectal cancer incidence rates for select cancer registries in IARC's Cancer Incidence in Five Continents, and trends in age-standardized death rates by single calendar year for select countries in the World Health Organization mortality database. In addition, available information regarding worldwide colorectal cancer screening initiatives are presented. The highest colorectal cancer incidence rates in 1998-2002 were observed in registries from North America, Oceania, and Europe, including Eastern European countries. These high rates are most likely the result of increases in risk factors associated with "Westernization," such as obesity and physical inactivity. In contrast, the lowest colorectal cancer incidence rates were observed from registries in Asia, Africa, and South America. Colorectal cancer mortality rates have declined in many longstanding as well as newly economically developed countries; however, they continue to increase in some low-resource countries of South America and Eastern Europe. Various screening options for colorectal cancer are available and further international consideration of targeted screening programs and/or recommendations could help alleviate the burden of colorectal cancer worldwide.
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                Author and article information

                Contributors
                shslyywzg@126.com
                Journal
                Cancer Med
                Cancer Med
                10.1002/(ISSN)2045-7634
                CAM4
                Cancer Medicine
                John Wiley and Sons Inc. (Hoboken )
                2045-7634
                24 April 2017
                June 2017
                : 6
                : 6 ( doiID: 10.1002/cam4.2017.6.issue-6 )
                : 1331-1340
                Affiliations
                [ 1 ] Department of General SurgeryShanghai Jiao Tong University Affiliated Sixth People's Hospital Shanghai 200233China
                [ 2 ] National Key Laboratory of Science and Technology on Nano/Micro Fabrication TechnologyResearch Institute Micro/Nano Science and Technology Shanghai Jiao Tong University Shanghai 200240China
                [ 3 ] Department of PathologyShanghai Jiao Tong University Affiliated Sixth People's Hospital Shanghai 200233China
                [ 4 ] Department of General SurgeryShanghai Jiao Tong University Affiliated Sixth People's Hospital Shanghai 200233China
                Author notes
                [*] [* ] Correspondence

                Zhigang Wang, Department of General Surgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, NO.600,YiShan Road, Shanghai 200233, China. Tel: 86‐021‐24058549; Fax: 86‐021‐24058549; E‐mail: shslyywzg@ 123456126.com

                [†]

                These authors contributed equally to this work

                Author information
                http://orcid.org/0000-0001-7555-1446
                Article
                CAM41029
                10.1002/cam4.1029
                5463071
                28440035
                b98813fa-d36b-4a3d-9b72-9090ac23223d
                © 2017 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

                This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

                History
                : 09 October 2016
                : 04 January 2017
                : 08 January 2017
                Page count
                Figures: 6, Tables: 0, Pages: 10, Words: 4443
                Funding
                Funded by: Shanghai Health and Family Planning Commission Research Projects
                Award ID: 20134024
                Funded by: National Natural Science Foundation of China
                Award ID: 81372311
                Categories
                Original Research
                Cancer Biology
                Original Research
                Custom metadata
                2.0
                cam41029
                June 2017
                Converter:WILEY_ML3GV2_TO_NLMPMC version:5.1.1 mode:remove_FC converted:08.06.2017

                Oncology & Radiotherapy
                colorectal cancer,cytoskeleton,migration,mir‐145
                Oncology & Radiotherapy
                colorectal cancer, cytoskeleton, migration, mir‐145

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