Differential expression of miR-1, a putative tumor suppressing microRNA, in cancer resistant and cancer susceptible mice
نویسندگان
چکیده
Mus spretus mice are highly resistant to several types of cancer compared to Mus musculus mice. To determine whether differences in microRNA (miRNA) expression account for some of the differences in observed skin cancer susceptibility between the strains, we performed miRNA expression profiling of skin RNA for over 300 miRNAs. Five miRNAs, miR-1, miR-124a-3, miR-133a, miR-134, miR-206, were differentially expressed by array and/or qPCR. miR-1 was previously shown to have tumor suppressing abilities in multiple tumor types. We found miR-1 expression to be lower in mouse cutaneous squamous cell carcinomas (cSCCs) compared to normal skin. Based on the literature and our expression data, we performed detailed studies on predicted miR-1 targets and evaluated the effect of miR-1 expression on two murine cSCC cell lines, A5 and B9. Following transfection of miR-1, we found decreased mRNA expression of three validated miR-1 targets, Met, Twf1 and Ets1 and one novel target Bag4. Decreased expression of Ets1 was confirmed by Western analysis and by 3' reporter luciferase assays containing wildtype and mutated Ets1 3'UTR. We evaluated the effect of miR-1 on multiple tumor phenotypes including apoptosis, proliferation, cell cycle and migration. In A5 cells, expression of miR-1 led to decreased proliferation compared to a control miR. miR-1 expression also led to increased apoptosis at later time points (72 and 96 h) and to a decrease in cells in S-phase. In summary, we identified five miRNAs with differential expression between cancer resistant and cancer susceptible mice and found that miR-1, a candidate tumor suppressor, has targets with defined roles in tumorigenesis.
منابع مشابه
Evaluation of MicroRNA-99a and MicroRNA-205 Expression Levels in Bladder Cancer
Bladder cancer is the second most common cancer in the genitourinary tract, showing often recurrence and progresse into invasive states. Epigenetic changes, such as microRNA alteration are involved in bladder cancer tumorigenesis through a variety of signaling pathways. The epigenetic state depends on geographic and lifestyle conditions. The aim of this study was to investigate the expression l...
متن کاملDifferential expression of miR-1297, miR-3191-5p, miR-4435, and miR-4465 in malignant and benign breast tumors
Objective(s): MicroRNAs (miRs) are a class of small non-coding RNAs which are associated with tumor growth and progression. In the present study, we assessed the expression of selected miRs in malignant, benign, and adjacent normal breast tissues. Materials and Methods: The expression of miR-1297, miR-3191-5P, miR-4435, and miR-4465 were...
متن کاملبررسی میزان بیان microRNA-146a در پولیپ های آدنوماتوز و سرطان کولورکتال
Background and purpose: Colorectal cancer (CRC) is one of the most common types of cancer. Its incidence has increased in Iran during the last 25 years. Micro-RNAs are used as new approach in cancer researches. The roles of miR-146a have been detected in different tumors. This study aimed at investigating the expression of microRNA146 in tumor tissue of colorectal adenocarcinoma in various stag...
متن کاملThe Effect of Endurance Training on MiR-155 Expression, STAT3 Gene Expression, and Interleukin 6 Protein in Mice with Breast Cancer
Background & Aims: Endurance training has an important role in the prevention and adjuvant therapy of breast cancer. The aim of the present study was to investigate the role of endurance training on miR- 155 expression, signal transducer and activator of transcription-3 (STAT3) gene expression, and interleukin 6 (IL-6) protein in breast cancer tumor in mice. Methods: In this study, 16 female Ba...
متن کاملStudy of the Expression of miR-4270 in Plasma of Patients with Breast Invasive Ductal Carcinoma
Detection of tumor-specific microRNAs (miRs) in the blood of cancer patients may provide a unique and valuable biomarker for diagnosis and prognosis. The aim of this study was to investigate whether plasma levels of microRNA-4270 could serve as a potential marker for breast invasive ductal carcinoma. A total of 40 breast cancer patients and 28 controls were recruited in this study. Total RNA wa...
متن کامل