Recent evidence highlights the crucial regulatory roles of long noncoding RNAs (lncRNA) in tumor biology. In colorectal cancer (CRC), the expression of several lncRNAs is dysregulated and play essential roles in CRC tumorigenesis. However, the potential biological roles and regulatory mechanisms of the novel human lncRNA, CASC2 (cancer susceptibility candidate 2), in tumor biology are poorly understood. In this study, CASC2 expression was significantly decreased in CRC tissues and CRC cell lines, and decreased expression was significantly more frequent in patients with advanced tumor-node-metastasis stage disease (TNM III and IV) (P = 0.028). Further functional experiments indicate that CASC2 could directly upregulate PIAS3 expression by functioning as a competing endogenous RNA (ceRNA) for miR-18a. This interactions leads to the de-repression of genes downstream of STAT3 and consequentially inhibition of CRC cell proliferation and tumor growth in vitro and in vivo by extending the G0/G1-S phase transition. Taken together, these observations suggest CASC2 as a ceRNA plays an important role in CRC pathogenesis and may serve as a potential target for cancer diagnosis and treatment.
MicroRNAs (miRNAs) are small noncoding RNAs that regulate gene expression post-transcriptionally. They are involved in almost all cellular processes, and many have been described as potential oncogenes or tumor suppressors. MicroRNA-373 (miR-373), which was first identified as a human embryonic stem cell (ESC)-specific miRNA, is suggested to be implicated in the regulation of cell proliferation, apoptosis, senescence, migration and invasion, as well as DNA damage repair following hypoxia stress. Deregulation of miR-373 has been demonstrated in a number of cancers, whether it acts as an oncogene or a tumor suppressor, however, seems to be context dependent. In this review, we focus on the diverse functions of miR-373 and its implication in cancers.
In addition to protein-coding genes, the human genome makes a large amount of noncoding RNAs. Long non-coding RNAs (lncRNAs) have been described as the largest subclass of the non-coding transcriptome in human noncoding RNAs. In recent years, lncRNAs have been considered to be the key regulators of tumor behavior. In this study, based on previous research, we investigated the expression and biological role of a newly identified cancer-related lncRNA, lncRNA-uc002kmd.1. We analyzed the relationship between lncRNA-uc002kmd.1 and colorectal cancer (CRC) in a total 45 CRC and paired adjacent, non-tumor tissue samples. We found that lncRNA-uc002kmd.1 expression was usually highly expressed in carcinoma compared with the tissue adjacent to the carcinoma. Through a series of experiments, the results showed that lncRNA-uc002kmd.1 regulates CD44 as a molecular decoy for miR211-3p. Our data indicated that the overexpression of lncRNA-uc002kmd.1 enhanced cell proliferation in CRC.
The social amoeba Dictyostelium discoideum is a simple but powerful model organism for the study of cell-cell adhesion molecules and their role in morphogenesis during development. Three adhesive systems have been characterized and studied in detail. The spatiotemporal expression of these adhesion proteins is stringently regulated, often coinciding with major shifts in the morphological complexity of development. At the onset of development, amoeboid cells express the Ca 2+-dependent cell-cell adhesion molecule DdCAD-1, which initiates weak homophilic interactions between cells and assists in the recruitment of individuals into cell streams. DdCAD-1 is unique because it is synthesized as a soluble protein in the cytoplasm. It is targeted for presentation on the cell surface by an unconventional protein transport mechanism via the contractile vacuole. Concomitant with the aggregation stage is the expression of the contact sites A glycoprotein csA ⁄ gp80 and TgrC1, both of which mediate Ca 2+ ⁄ Mg 2+-independent cell-cell adhesion. Whereas csA ⁄ gp80 is a homophilic binding protein, TgrC1 binds to a heterophilic receptor on the cell. During cell aggregation, csA ⁄ gp80 associates preferentially with lipid rafts, which facilitate the rapid assembly of adhesion complexes. TgrC1 is synthesized at low levels during aggregation and rapid accumulation occurs initially in the peripheral cells of loose mounds. The extracellular portion of TgrC1 is shed and becomes part of the extracellular matrix. Additionally, analyses of knockout mutants have revealed important biological roles played by these adhesion proteins, including size regulation, cell sorting and cell-type proportioning.
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