Tumor breakthrough is driven by genetic or epigenetic variations which assist in initiation, migration, invasion and metastasis of tumors. Astrocyte elevated gene-1 (AEG-1) protein has risen recently as the crucial factor in malignancies and plays a potential role in diverse complex oncogenic signaling cascades. AEG-1 has multiple roles in tumor growth and development and is found to be involved in various signaling pathways of: (i) Ha-ras and PI3K/AKT; (ii) the NF-κB; (iii) the ERK or mitogen-activated protein kinase and Wnt or β-catenin and (iv) the Aurora-A kinase. Recent studies have confirmed that in all the hallmarks of cancers, AEG-1 plays a key functionality including progression, transformation, sustained angiogenesis, evading apoptosis, and invasion and metastasis. Clinical studies have supported that AEG-1 is actively intricated in tumor growth and progression which includes esophageal squamous cell, gastric, colorectal, hepatocellular, gallbladder, breast, prostate and non-small cell lung cancers, as well as renal cell carcinomas, melanoma, glioma, neuroblastoma and osteosarcoma. Existing studies have reported that AEG-1 expression has been induced by Ha-ras through intrication of PI3K/AKT signaling. Conversely, AEG-1 also activates PI3K/AKT pathway and modulates the defined subset of downstream target proteins via crosstalk between the PI3K/AKT/mTOR and Hedgehog signaling cascade which further plays a crucial role in metastasis. Thus, AEG-1 may be employed as a biomarker to discern the patients of those who are likely to get aid from AEG-1-targeted medication. AEG-1 may play as an effective target to repress tumor development, occlude metastasis, and magnify the effectiveness of treatments. In this review, we focus on the molecular mechanism of AEG-1 in the process of carcinogenesis and its involvement in regulation of crosstalk between the PI3K/AKT/mTOR and Hedgehog signaling. We also highlight the multifaceted functions, expression, clinicopathological significance and molecular inhibitors of AEG-1 in various cancer types.

Background: MicroRNA, a non-coding RNA molecule plays a vital role in post transcriptional gene expression. MicroRNA-122, a liver specific microRNA was found to be downregulated in liver cancer and it’s associated with hepatocarcinogenesis. Being confirmed as tumor suppressor microRNA in liver carcinogenesis, we aimed to study the expression of microRNA-122 in Colon cancer cell lines and also the role of microRNA-122 in cell proliferation, invasion and migration of colon cancer cells. Methods: The expression of microRNA-122 is quantified using qRT-PCR by TaqMan universal primers. Colon cancer cell lines (SW480, SW620, HCT116) were transfected with microRNA-122 mimics and further studied for determining cell proliferation using CCK-8 kit, migration using Scratch assay, invasion using Transwell assay, apoptosis using Annexin-V FITC kit, and also gene expression. Results: Gene expression results displayed decreased expression microRNA-122 in colon cancer cell lines. Transfection with microRNA-122 mimics impaired the cell proliferation and migration compared with control. FACS analysis confirmed that the percentage of microRNA-122 mimic transfected cells undergoing early apoptosis was increased. Gene expression of AEG-1, PI3K, CDK6, PCNA were found to be downregulated in microRNA-122 overexpressed cells. Migratory and invasion potential of transfected cells was lessened in mimic transfected cells compared to control. Conclusion: The overexpression of microRNA-122 inhibited the cellular proliferation, migration, invasion and increased percentage of cells undergoing early apoptosis suggesting its anti-cancer potential. Studying the role of microRNA-122 and its interactions with oncogenes might pave a way to understand the underlying mechanism in colon cancer.

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: MicroRNAs (miRS) are a class of small non-coding RNAs which perform a crucial function in posttranscriptional gene regulation. Dysregulation of this microRNAs are associated with many types of cancer progression. In tumorigenesis, downregulated microRNAs might function as tumour suppressor by repressing onco- genes, whereas overexpressed miRs might function as oncogenes by suppressing tumour suppressor. Similarly, Metadherin (also known AEG-1/ LYRIC), is an oncogene, whose levels are found to be very high in various cancers and plays a crucial role in proliferation of cells and invasion. Our review focuses on the study which shows alteration of microRNA expression profile and suppression of carcinogenesis when MTDH/AEG-1 is targeted. It summarises about the studies where downregulation and upregulation AEG-1 and microRNAs respectively, alter the biological functions of the cell, such as proliferation and apoptosis. Studies have reported that AEG-1 can be direct or indirect target of microRNA which could provide a new-insight to know the underlying molecular mechanism and might contribute to the progress of new therapeutic strategies for the disease.

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