Background: MicroRNA (miRNA) is a kind of non-coding RNA that regulates gene expression and is involved in tumor development. MiRNA-125 is reportedly aberrantly expressed in colorectal cancer tissue; however, its potential function and underlying mechanism remain unclear. The present study aimed to investigate the expression level and potential role of the miRNA-125 family in the invasion and migration of colorectal cancer. Methods:To further understand the role of the miRNA-125 family in metastatic colorectal cancer, we overexpressed miRNA-125 in the SW480 cell line by transfection with the miRNA-125 family mimics or a sponge. Methyl thiazolyl tetrazolium (MTT) assay was performed to identify the effect of the miRNA-125 family on cell proliferation, and a Transwell filter assay was used to detect the role of the miRNA-125 family in migration and invasion. A luciferase assay was carried out to confirm the binding site of miRNA-125 and the target gene, damage specific DNA binding protein 2 (DDB2). Western blot was applied to detect the expression levels of DDB2 and the markers of epithelial-to-mesenchymal transition (EMT) in colorectal cancer cells. Results:The real-time polymerase chain reaction (PCR) results showed that miR-125a-5p and miR-125b-1-5p were up-regulated in metastatic colorectal cancer tissues. The Transwell filter assay results appeared that miR-125a-5p and miR-125b-1-5p could promote the invasion and migration of colorectal cancer cells. The luciferase assay data confirmed the binding site of miR-125a-5p and miR-125b-1-5p on the 3' untranslated region (3'UTR) of DDB2 messenger RNA (mRNA). The real-time PCR and Western blot results indicated that miR-125a-5p and miR-125b-1-5p could regulate the expression levels of DDB2 and EMT markers, and lower DDB2 expression was observed in metastatic tissues.Conclusions: Our findings illustrated that miRNA125a-5p and miRNA125b-1-5p could reduce the expression of DDB2 by binding to the 3'UTR region, and then regulate the expression levels of EMT markers, leading to the enhanced invasion and metastasis of colorectal cancer cells. Thus, miRNA125a-5p and miRNA125b-1-5p might be novel markers of colorectal cancer migration and potential therapeutic targets to treat metastatic colorectal cancer patients. Highlight box Key findings• The miRNA125a-5p and miRNA125b-1-5p could reduce the expression of DDB2 by binding to the 3'UTR region, and then regulate the expression levels of EMT markers, leading to the enhanced invasion and metastasis of colorectal cancer cells. What is known and what is new?• MiRNA-125 is reportedly aberrantly expressed in colorectal cancer tissue; • The present study explained the mechanism of miRNA-125 family regulated invasion and migration of colorectal cancer. What is the implication, and what should change now?• The miRNA125a-5p and miRNA125b-1-5p might be novel markers of colorectal cancer migration and potential therapeutic targets to treat metastatic colorectal cancer patients.

IntroductionThe global incidence of patients with type 2 diabetes mellitus (T2DM) with dry eye is increasing annually, which imposes additional healthcare costs and financial burden on families and societies. In clinical practice, artificial tears are often used for symptomatic treatment, but these can only relieve the symptoms of discomfort. Acupuncture is a widely used alternative therapy. Indeed, randomised trials have found that acupuncture confers a definite therapeutic effect on patients with T2DM with dry eye. However, systematic reviews on the effectiveness and safety of acupuncture are lacking, therefore this systematic review aims to evaluate the effectiveness and safety of acupuncture for T2DM with dry eye.Methods and analysisFour English databases (PubMed, Cochrane Library, Embase and Ovid), three Chinese databases (China National Knowledge Infrastructure, Wanfang, Chonqing VIP Information), three Japanese databases (Japan Science, Technology Agency and Japan Medical Abstracts Society) and three Korean databases (Korean Medical database, Oriental Medicine Advanced Searching Integrated System and Research Information Service System) will be searched for reports published between 1 January 2007 and 1 October 2021. Only randomised controlled trials will be included, and language or publication dates will not be restricted. Two researchers will independently extract, manage and analyse data. The primary outcomes will include Schirmer’s I test, breakup time, corneal fluorescein staining and ocular surface disease index scores. Secondary results will include visual analogue scale scores for ocular symptoms and any adverse events related to acupuncture. We will use Review Manager V.5.4 for the meta-analysis. The risk of bias will be independently assessed using Cochrane’s ‘risk of bias’ tool.Ethics and disseminationEthical approval will not be required since raw data will not be collected or generated. Our findings will be disseminated through peer-reviewed journal.PROSPERO registration numberCRD42021271891.