BackgroundMicroRNAs (miRNAs) are important regulators that play key roles in tumorigenesis and tumor progression. A previous report has shown that let-7 family members can act as tumor suppressors in many cancers. Through miRNA array, we found that let-7f was downregulated in the highly metastatic potential gastric cancer cell lines GC9811-P and SGC7901-M, when compared with their parental cell lines, GC9811 and SGC7901-NM; however, the mechanism was not clear. In this study, we investigate whether let-7f acts as a tumor suppressor to inhibit invasion and metastasis in gastric cancers.Methodology/PrincipalReal-time PCR showed decreased levels of let-7f expression in metastatic gastric cancer tissues and cell lines that are potentially highly metastatic. Cell invasion and migration were significantly impaired in GC9811-P and SGC7901-M cell lines after transfection with let-7f-mimics. Nude mice with xenograft models of gastric cancer confirmed that let-7f could inhibit gastric cancer metastasis in vivo after transfection by the lentivirus pGCsil-GFP- let-7f. Luciferase reporter assays demonstrated that let-7f directly binds to the 3′UTR of MYH9, which codes for myosin IIA, and real-time PCR and Western blotting further indicated that let-7f downregulated the expression of myosin IIA at the mRNA and protein levels.Conclusions/SignificanceOur study demonstrated that overexpression of let-7f in gastric cancer could inhibit invasion and migration of gastric cancer cells through directly targeting the tumor metastasis-associated gene MYH9. These data suggest that let-7f may be a novel therapeutic candidate for gastric cancer, given its ability to reduce cell invasion and metastasis.

Early growth response 1 (EGR1) is a multifunctional transcription factor; Positive and negative functions of EGR1 in various tumors rely on the integrated functions of various genes it regulates. In this study, we observed the role of EGR1 in non-small-cell lung carcinoma (NSCLC) and identified genes that influence cell fate and tumor development. Various assays showed that EGR1 arrested cell mobility, inhibited migration, and induced apoptosis. Microarray analysis revealed that 100 genes, including CDKN1C, CDC27 and PRKDC, changed their mRNA expressions with the increase of EGR1 and contributed to intervention of tumor progression. Bioinformatics analysis and promoter analysis indicated that an EGR1 binding site was situated in the promoter of KRT18 (also named CK18) and KRT18 could assist in inhibition of NSCLC development. The expression level of EGR1 and KRT18 in NSCLC clinical cases was investigated by immunohistochemistry, in which the protein expression of KRT18 was found to be significantly associated with EGR1 and lymph node metastasis. The results collectively confirm that EGR1 functions as a tumor suppressor in NSCLC. This study is the first to report KRT18 expression is directly regulated by EGR1, and contributes to decrease malignancy of NSCLC.

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These results suggest that DBC1 is over-expressed in colorectal cancer and that it might serve as a predictor for selecting patients at high risk of poor prognosis.

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Context.-The expression of membrane-bound complement regulatory proteins (mCRPs) that inhibit the complement system in normal tissues is essential for selfprotection against an autologous immune reaction. However, the expression patterns of mCRPs, including CD46, CD55, and CD59, are inconsistent in different types of cancer cells.Objectives.-To determine whether CD46, CD55, and CD59 are differentially expressed in neoplastic and adjacent normal colon tissues and to assess their clinical significance.Design.-Immunohistochemistry was performed on tissue microarrays of cancerous and adjacent normal colon tissues.Results.-The expression levels of CD46, CD55, and CD59 were significantly higher in colon cancer tissues compared with the normal adjacent colon tissues. We found that the expression levels of CD55 and CD59 correlated with the grade of differentiation in colon cancers. In addition, the expression of CD55 and CD59 was greater in stage III and stage IV colon cancers than in stage I and stage II cancers according to staging by the TNM classification.Conclusions.-CD46, CD55, and CD59 are up-regulated in colon cancer. Specifically, CD55 and CD59 are of clinical relevance to differentiation and TNM staging of colon cancer. These data suggest that CD46, CD55, and CD59 have the potential to be used for molecular staging diagnoses and for colon cancer therapies.(Arch Pathol Lab Med. 2014;138:910-919; doi: 10.5858/ arpa.2013-0064-OA) I mmunotherapies using monoclonal antibodies (mAbs) have attracted great attention from oncologists because these mAbs can be used to directly or indirectly damage tumor cells, while sparing normal, healthy cells. In addition, complement activation by mAbs can mediate direct tumor cell lysis or antibody-dependent cell-mediated cytotoxicity. Specifically, complement activation results in the formation of C3-convertase and C5-convertase, and the cleavage of C3 leads to the generation of C3b, which attaches to the cell surface and causes amplification of the complement cascade. Cleavage of C5 by C5-convertase results in fragmentation of C5 into C5a and C5b, C5b could form a complex with C6 and C7 at the membrane surface (C5b-7 complex), and C5b-7 complex binds C8abc to form the C5b-8 complex, which ultimately binds sequentially to multiple copies of C9 to form the mature membrane attack complex. The membrane attack complex then leads to direct complement-dependent cytotoxicity (CDC) through the formation of membranepenetrating pores.1 Because the targeting of cells by CDC is destructive and irreversible, complement activation is tightly regulated by complement regulatory proteins (CRPs) to avoid uncontrolled activation and an autologous immune reaction. Complement regulatory proteins exist as soluble proteins or as membrane-bound CRPs (mCRPs). The mCRPs include mainly CD46, CD55, and CD59. Also called membrane cofactor protein (MCP), CD46 is the cofactor for factor I-mediated degradation of C3b and C4b, which prevents the continuous formation of convertases. Decayaccelerating factor, also k...

OPN is upregulated in liver tissues and plasma of cirrhotic patients and promotes TGF-β1 mediated HSC activation.

Our findings emphasize the important role of Ran in differentiation, disease stage, and metastasis in human CRC. Ran may play an important role in the development of CRC and may serve as a novel prognostic indicator of CRC.