BackgroundLong noncoding RNAs (lncRNAs) have emerged recently as a new class of genes that regulate cellular processes, such as cell growth and apoptosis. The SPRY4 intronic transcript 1 (SPRY4-IT1) is a 708-bp lncRNA on chromosome 5 with a potential functional role in tumorigenesis. The clinical significance of SPRY4-IT1 and the effect of SPRY4-IT1 on cancer progression are unclear.MethodsQuantitative reverse transcriptase PCR (qRT-PCR) was performed to investigate the expression of SPRY4-IT1 in 48 breast cancer tissues and four breast cancer cell lines. Gain and loss of function approaches were used to investigate the biological role of SPRY4-IT1 in vitro. Microarray bioinformatics analysis was performed to identify the putative targets of SPRY4-IT1, which were further verified by rescue experiments, and by western blotting and qRT-PCR.ResultsSPRY4-IT1 expression was significantly upregulated in 48 breast cancer tumor tissues comparedwith normal tissues. Additionally, increased SPRY4-IT1 expression was found to be associated with a larger tumor size and an advanced pathological stage in breast cancer patients. The knockdown of SPRY4-IT1 significantly suppressed proliferation and caused apoptosis of breast cancer cells in vitro. Furthermore, we discovered that ZNF703 was a target of SPRY4-IT1 and was downregulated by SPRY4-IT1 knockdown. Moreover, we provide the first demonstration that ZNF703 plays an oncogenic role in ER (−) breast carcinoma cells.ConclusionsSPRY4-IT1 is a novel prognostic biomarker and a potential therapeutic candidate for breast cancer.Electronic supplementary materialThe online version of this article (doi:10.1186/s12943-015-0318-0) contains supplementary material, which is available to authorized users.

BackgroundAberrant expression of long noncoding RNAs (lncRNAs) has frequently been reported in cancer studies, including those of colorectal cancer (CRC). Increasing evidence suggests that lncRNAs are significantly correlated with the pathogenesis, development and metastasis of cancer. Loc554202 is a 2166-bp transcript on human chromosome 9p21.3, the expression of which is dysregulated in breast and lung cancer cells. However, its role in CRC remains under investigation.MethodsQuantitative real-time polymerase chain reaction (qRT-PCR) was carried out to assess the relative expression of Loc554202 in CRC cell lines and tissues. Gain and/or loss of function approaches were used to investigate the potential functional roles in cell proliferation and apoptosis in vitro and in vivo. qRT-PCR, western-blotting and immunohistochemistry were used to evaluate the mRNA and protein expression of apoptosis-related factors.ResultsLoc554202 was significantly downregulated in cancerous tissues and CRC cell lines compared with adjacent normal tissue and a normal human intestinal epithelial cell line. Low Loc554202 expression was closely associated with advanced pathologic stage and a larger tumor size. The overexpression of Loc554202 decreased the cell proliferation and induced apoptosis in vitro and hindered tumorigenesis in vivo. Loc554202 regulated cell apoptosis partly through the activation of specific caspase cleavage cascades.ConclusionOur results suggest that Loc554202 may play an important role in the progression of CRC and could be a candidate prognostic biomarker or a target for new cancer therapies.Electronic supplementary materialThe online version of this article (doi:10.1186/s13046-015-0217-7) contains supplementary material, which is available to authorized users.

Accumulating evidence strongly suggests that dysregulation of long noncoding RNAs (lncRNAs) is associated with human carcinogenesis. The lncRNA HOXA transcript at the distal tip (HOTTIP) is involved in the development of several cancers. However, the biological role of HOTTIP in colorectal cancer (CRC) has not yet been discussed. Here, we report that HOTTIP acts as a functional oncogene in the pathogenesis of CRC. In this study, quantitative polymerase chain reaction (qPCR) was performed to detect the expression of HOTTIP in 48 pairs of colorectal cancer samples. We found that overexpression of HOTTIP is correlated with an advanced pathological stage and a larger tumor size. Moreover, functional analyses revealed that the knockdown of HOTTIP expression by small interfering RNA (siRNA) or small hairpin RNA (shRNA) could inhibit cell proliferation and induce cell apoptosis. More importantly, we observed that HOTTIP knockdown induced a marked increase in the number of cells in the G0/G1 phase and a reduction in the number of cells in the S phase in both DLD-1 cells and SW480 cells. An in vivo experiment also revealed that the knockdown of HOTTIP inhibited tumor growth. Western blot and immunohistochemistry analyses indicated that HOTTIP potentially contributed to CRC cell growth partially through the silencing of p21 expression. Collectively, our results suggest that HOTTIP is involved in the progression of CRC and may provide evidence for HOTTIP being a target for therapy of this disease.

LncRNA PTENP1 is a competitive endogenous RNA (ceRNA) involved in decoying miR-106b in multiple diseases. This study investigates the interaction of PTENP1 and miR-106b in cell proliferation, apoptosis and epithelial-mesenchymal transition (EMT) in cervical cancer. The expressions of PTENP1, miR-106b and PTEN were determined in cervical cancer tissues, adjacent normal tissues, cervical cancer cells (HeLa, SiHa, C33A and CasKi) and normal cervical epithelial H8 cells. Up-regulation of PTENP1 and down-regulation of miR-106b were conducted in HeLa and CasKi cells by transfecting cells with corresponding miRNA mimics and inhibitors. Bioinformatics analysis, luciferase reporter assay and RNA-pull down assay were performed to verify the association of miR-106b, PTEN, and PTENP1. Cell growth and cell apoptosis were determined by CCK-8 and flow cytometry analysis. It was found that the expressions of PTENP1 and PTEN were up-regulated and that of miR-106b were down-regulated in cervical cancer tissues and cells. PTENP1 localized in cytoplasm and competitively bound to miR-106b. Up-regulation of PTENP1 and down-regulation of miR-106b contributed to increased expressions of PTEN and E-cadherin. Decreased expression of miR-106b, ZEB1, Snail and Vimentin, resulted in inhibiting cell proliferation and promoting cell apoptosis. Over-expression of PTENP1 and miR-106b accelerated cell proliferation and slowed down cell apoptosis. miR-106b inhibited the expression of PTEN. Our results suggest that LncRNA PTENP1 inhibits cervical cancer progression by competitively binding to miR-106b, leading to promote PTEN expression, inhibit cell proliferation and EMT and induce cell apoptosis in cervical cancer cells ARTICLE HISTORY

Objective: There have been inconsistent results published regarding the relationship between dyslipidaemia and an increased risk of colorectal neoplasia (CRN), including colorectal adenoma (CRA) and colorectal cancer (CRC). We conducted a meta-analysis to explore the relationship between dyslipidaemia and CRN. Design: We identified studies by performing a literature search using PubMed, EMBASE and the Science Citation Index through October 2013. Setting: We analysed thirty-three independent studies reporting the association between CRN and at least one of the selected lipid components, including total cholesterol (TC), TAG, HDL-cholesterol (HDL-C) and LDL-cholesterol (LDL-C). Subjects: CRN cases (n 21 809) were identified. Results: Overall, people with high levels of serum TAG (risk ratio (RR) = 1·08; 95 % CI 1·05, 1·12, P < 0·00001) and LDL-C (RR = 1·07; 95 % CI 1·00, 1·14, P = 0·04) presented an increased prevalence of CRN. Subgroup analyses revealed that high levels of serum TC (RR = 1·04; 95 % CI 1·01, 1·09, P = 0·02), TAG (RR = 1·06; 95 % CI 1·03, 1·10, P = 0·0009) and LDL-C (RR = 1·11; 95 % CI 1·04, 1·19, P = 0·003) increased the risk of CRA but not of CRC. No association between serum HDL-C and risk for CRN (including CRA and CRC) was observed. Conclusions: Both TAG and LDL-C were significantly associated with an increasing prevalence of CRN. High levels of serum TC, TAG and LDL-C were positively associated with CRA but not with CRC. No significant association was observed between levels of serum HDL-C and CRN. Keywords Serum lipids Colorectal adenomaColorectal cancer TAG Meta-analysis Colorectal cancer (CRC) is reported to be the fourth most commonly diagnosed cancer and is the second most common cause of cancer deaths in North America (1) . CRC is believed to arise from colorectal adenoma (CRA) through a sequence from adenoma to adenocarcinoma as a consequence of a limited set of molecular events that largely originate with a relatively benign adenoma that progresses to cancer (2) . Accumulated data indicate that metachronous lesions occur at a rate of 20 to 30 % per year in post-polypectomy patients. The propensity to develop CRA identifies a sizeable subgroup of the population at an enhanced risk for subsequent adenoma formation and colorectal carcinoma. This indicates that identifying risk factors associated with CRN is essential for the reduction of colorectal carcinoma.The positive association between obesity and CRA prevalence demonstrates an underlying dose-response relationship according to BMI (3) . Timely screening of obese patients for CRA is thus recommended. Dyslipidaemia is an important component of metabolic syndrome and is demonstrated to contribute to colorectal tumorigenesis through insulin resistance, oxidative stress and inflammatory † The first three authors contributed equally to this work.