Ovarian cancer (OC) remains one of the most common types of malignant cancer, and the molecular mechanism underlying its proliferation is still largely unclear. It is reported that microRNAs acted as important regulators of cell proliferation by regulating its targeted gene. In this study, our result showed that miR-572 was markedly upregulated in OC cell lines and clinical tissues. Results of both gain-of-function and loss-of-function experiments revealed that upregulation of miR-572 expression dramatically promoted OC cell proliferation, whereas decreased miR-572 expression significantly reduced cell proliferation. Bioinformatics analysis and luciferase reporter assays further revealed PPP2R2C, a putative tumor suppressor as a potential target of miR-572. Moreover, silencing of PPP2R2C using small interfering RNA (siRNA) counteracted the proliferation arrest by miR-572-in in OC cells. In sum, our data provide that miR-572 promoted cell proliferation in OC by targeting PPP2R2C and might serve as a therapeutic target of OC.

Aberrantly expressed microRNAs (miRNAs) are involved in oral tumorigenesis since they can alter the expression of proteins involved in cancer progression. It remains unclear whether miRNA-221 influences the resistance of human oral squamous cell carcinoma cells to Adriamycin. We therefore investigated the role of miR-221 in the sensitivity of oral squamous cell carcinoma cells to chemotherapy. Tca8113 and UM2 cells were treated with different concentrations of Adriamycin. Quantitative real-time PCR (qRT-PCR) revealed miR-221 upregulation after Adriamycin treatment of Tca8113 and UM2 cells. By using miR-221 inhibitor mimics, we found that depleting cells of miR-221 increases the sensitivity of the cells to Adriamycin. The expression of tissue inhibitor of metalloproteinase-3 (TIMP3), a target of miR-221, was decreased in cells treated with Adriamycin. TIMP3 depletion reversed the effect of a miR-221 inhibitor mimics on cell survival rates and apoptosis. Together, these results reveal that silencing of miR-221 enhances the sensitivity of human oral squamous cell carcinoma cells to Adriamycin through upregulation of TIMP3 expression.

Activator of 90kDa heat shock protein ATPase homolog 1 (AHSA1) is a chaperone of heat shock 90kDa (HSP90) and stimulates ATPase activity of HSP90. The function of AHSA1 in osteosarcoma (OS) has not been reported yet. A previous study showed AHSA1 was overexpressed in OS cells. In this study, we investigated the role of AHSA1 in OS cells by silencing AHSA1. We report that silencing AHSA1 inhibited cell growth, migration, and invasion, and increased apoptosis of MG-63 and Saos2 cells. We also found that silencing AHSA1 decreased the ATPase activity of HSP90 in OS cells. In addition, silencing AHSA1 increased the levels of negative regulators of Wnt/β-catenin signalling pathway, Axin-2 and GSK3β, and decreased the levels of two key members of Wnt/β-catenin signalling pathway, namely, Wnt-5a and β-catenin. In conclusion, silencing AHSA1 regulates cell growth, apoptosis, migration, and invasion by regulating Wnt/β-catenin signalling pathway and their negative regulators.

Tamoxifen (TAM) and fulvestrant (FUL) represent the major adjuvant therapy to estrogen receptor-alpha positive (ER(+)) breast cancer patients. However, endocrine resistance to TAM and FUL is a great impediment for successful treatment. We hypothesized that miR-21 might alter the sensitivity of breast cancer cells to TAM or FUL by regulating cell autophagy. Using the ER(+) breast cancer cells, we knockdown miR-21.by transfection with miR-21 inhibitor, then the cells were exposed to TAM or FUL and the percentages of apoptosis and autophagy were determined. Knockdown of miR-21 significantly increased the TAM or FUL-induced apoptosis in ER(+) breast cancer cells. Further, silencing of miR-21 in MCF-7 cells enhanced cell autophagy at both basal and TAM or FUL-induced level. The increase of autophagy in miR-21-knockdown MCF-7 cells was also indicated by increase of beclin-1, LC3-II and increased GFP-LC3 dots. Importantly, knockdown of miR-21 contributed to autophagic cell death, which is responsible for part of TAM induced cell death in miR-21 inhibitor-transfected cells. Further analysis suggested that miR-21 inhibitor enhance autophagic cell death through inhibition of PI3K-AKT-mTOR pathway. MiR-21 coordinated the function of autophagy and apoptosis by targeting Phosphatase and tensin homolog (PTEN) through inhibition of PI3K-AKT-mTOR pathway. In conclusion, silencing of miR-21 increased the sensitivity of ER(+) breast cancer cells to TAM or FUL by increasing autophagic cell death. Targeting autophagy-related miRNAs is a potential strategy for overcoming endocrine resistance to TAM and FUL.

MiRNAs, as oncogenes or as anti-oncogenes, play critically regulated roles in human cancers at posttranscriptional level. A number of dysregulated miRNAs has been observed in HCC. However, the expression and function of miR-670-5p have not been evaluated in HCC to date. In this study, we examined and confirmed the over-expression of miR-670-5p in HCC and in hepatoma-derived cells Hep3B. At least 60% of HCC tissues showed a greater than three-fold enhance in the expression of miR-670-5p compared with paired adjacent non-cancerous tissues. Knockdown studies for miR-670-5p showed that the expression of miR-670-5p promoted cellular proliferation. In tissues and cells with high expression of miR-670-5p, decreased expression of PROX1, a miR-670-5p predicated target, was detected. It confirmed that PROX1 expression was obviously affected by the expression of miR-670-5p. Furthermore, overexpression of PROX1 greatly inhibitted cellular proliferation. Therefore, it was inferred that miR-670-5p may play important roles in enhancing proliferation activity that is associated with HCC by modulating PROX1 expression at posttranscriptional level.

TKI-acquired resistance is a tough obstacle for effectively treating NSCLC patients with EGFR mutant characteristics. T790M mutations and MET amplifications account for 70% of the acquired resistance, but the causes for the remaining 30% need elucidation.

Lung cancer's dismal prognosis led to new therapeutic approaches among which TKIs being among most promising;

Malignant pleural mesothelioma (MPM) is a rare malignancy, with extremely poor survival rates. There are limited treatment options, with no second line standard of care for those who fail first line chemotherapy. Recent advances have been made to characterise the underlying molecular mechanisms of mesothelioma, in the hope of providing new targets for therapy. With the discovery that non-coding regions of our DNA are more than mere junk, the field of research into non-coding RNAs (ncRNAs) has exploded in recent years. Non-coding RNAs have diverse and important roles in a variety of cellular processes, but are also implicated in malignancy. In the following review, we discuss two types of non-coding RNAs, long non-coding RNAs and microRNAs, in terms of their role in the pathogenesis of MPM and their potential as both biomarkers and as therapeutic targets in this disease.

MET amplification, protein expression, and splice mutations at exon 14 are known to cause dysregulation of the MET/HGF pathway. Our study aimed to confirm the relationship among MET amplification, protein expression, and mutations in pulmonary adenocarcinoma.

Cellular-mesenchymal-epithelial transition (MET) protein has recently been identified as a novel target that shows promise for the treatment of non-small-cell lung cancer (NSCLC). However, the relationship between de novo MET expression and patient outcomes remains unclear.

Genomic aberrations involving ALK, ROS1 and MET can be driver oncogenes in lung adenocarcinomas. Identification of tyrosine kinase inhibitors (TKIs) with activity against these tumors and of preclinical systems to model response are warranted.

To explore the effect of lycorine in inducing apoptosis of pulmonary carcinoma cell A549 and its mechanism. In the study, pulmonary carcinoma cell A549 were taken as the experimental subject and processed with different concentrations of lycorine (0, 0.5, 1.0, 2.0, 4.0 and 8.0 μmol x L(-1)). The MTT method was used to observe the cell proliferation. The apoptosis rate of A549 cells was determined by Annexin FITC/PI double staining. The microplate reader was used to detect the activities of Bcl-2, Bax and p53. The changes in mitochondrial membrane potential were measured by the flow cytometry. The expressions of apoptosis-related factors Bcl-2, Bax, p53 and Survivin were determined by Real-time PCR. The results showed that lycorine significantly inhibited the proliferation of A549 cells (P < 0.05), induced the apoptosis on A549 cells (P < 0.05), increased the activities of Bax and p53, reduced Bcl-2 activity and mitochondrial membrane potential, and notably changed the gene expressions of Bcl-2, Bax, p53 and Survivin (P < 0.05). In conclusion, lycorine can induce the apoptosis of A549 cells and be applied to treat pulmonary carcinoma. Its mechanism may be related to the activation of relevant factors in Bcl-2 signaling pathway.

To study the effect of sodium aescinate in inducing human breast cancer MCF-7 cells apoptosis and its possible mechanism. MTT assay was used to detect the inhibitory effect of sodium aescinate on the proliferation of MCF-7 cells. The morphological changes were observed under inverted microscope. DAPI nuclear staining was used to detect the changes in cell nucleus. Annexin V-FITC/PI flow cytometry was adopted to test the apoptosis rate. Changes in apoptosis-related proteins (PARP, cleaved caspase-8 and pro-caspase-3), cell survival-associated signal molecules (AKT and ERK) and their common upstream kinase SRC was detected by Western blotting. The result showed that after different concentrations of sodium aescinate were used to treat breast cancer MCF-7 cells, they inhibited the proliferation of MCF-7 cells in a dose-dependent manner, induced cell apoptosis (typical morphological changes in nucleus, significant increase in cell apoptosis rate). The expressions of cleaved PARP and caspase-8 increased, while the expression of pro-caspase-3 decreased, which further verified sodium aescinate's effect in inducing cell apoptosis. Sodium aescinate significantly inhibited the phosphorylation of cell survival-related signal molecules (AKT, ERK) and down-regulate the activation of their common up-stream kinase SRC. The findings indicated that sodium aescinate can block signals transiting to downstream molecules AKT, ERK, inhibit the proliferation of breast cancer cell MCF-7 cell apoptosis and induced cell apoptosis by suppressing the activation of SRC.

Evodiamine is one of the most important antitumor alkaloid from evodiamine. This study focused on the mechanism of evodiamine in inducing apoptosis of gastric cancer SGC-7901 cells through mammalian target of rapamycin (mTOR) signal pathway, in order to explore its antitumor mechanism and lay a foundation for clinical treatment of gastric cancer. The sole cytotoxic effect of evodiamine on SGC-7901 cells and human peripheral blood mononuclear cells (PBMCs) was observed by MTT assay. After the cells were respectively intervened with single evodiamine or evodiamine combined with z-VAD-fmk, the gene expressions of mTOR, p70S6K and 4EBP1 were analyzed by real-time PCR, and the protein expressions of mTOR and p-mTOR were detected by western blot. The result showed that evodiamine inhibited the apoptosis of SGC-7901 cells in a time-dependent manner, with no cytotoxic effect on human PBMCs. After the respective intervention with single evodiamine or evodiamine combined with z-VAD-fmk, the cells became round and floated in medium. Compared with the control group, both treatment methods can inhibit mTOR, 4E-BP1 and p70S6K gene expressions, with significant differences. Compared with single evodiamine, evodiamine combined with z-VAD-fmk showed a higher inhibitory rate in gene expression. According to the Western Blot result, evodiamine can inhibit the protein expressions of mTOR and p-mTOR regardless of the combination with z-VAD-fmk, with a higher inhibitory rate after z-VAD-fmk blocked caspase. In conclusion, evodiamine may promote the apoptosis of SGC-7901 cells through mTOR signal pathway.

The prognostic factors of the fibroblast growth factor receptor 1 (FGFR1) in non-small cell lung cancer (NSCLC) remain controversial.

Oral squamous cell carcinoma (OSCC), the most frequent of all oral cancers, is a type of highly malignant tumors with a high capacity to invade locally and form distant metastases. An increasing number of studies have shown that microRNAs (miRNAs) play an important role in regulating cancer metastasis and invasion. In the present study, we detected the expression of miR-221 in two highly metastatic OSCC cell lines and two OSCC cell lines that are less metastatic using quantitative real-time PCR analysis (qRT-PCR). The qRT-PCR results indicate that miR-221 is upregulated in highly metastatic OSCC cell lines. Then, miR-221 expression was knocked down by transfection with miR-221 inhibitor, and UM1 cell migration and invasion were assessed using transwell migration and invasion assays. The results indicate that inhibition of miR-221 suppressed migration and invasion of UM1 cells. Furthermore, methyl-CpG binding domain protein 2 (MBD2) was identified as a direct target gene of miR-221. Additionally, MBD2 silencing could partly reverse the effect of miR-221 on cell migration and invasion. In conclusion, downregulation of miR-221 inhibits cell migration and invasion at least partially through targeting MBD2 in the human OSCC cell line UM1.

Prostate cancer is a common cancer in men. Genetic variations in inflammatory response genes can potentially influence the risk of prostate cancer. We aimed to examine the association between PPARG Pro12Ala, NFKB1 -94 ins/del, NFKBIA -826C/T, COX-1 (50C>T), and COX-2 (-1195G>A) polymorphisms on prostate cancer risk. The genotypes of the polymorphisms were ascertained in 543 prostate cancer patients and 753 controls through PCR-RFLP and the risk association was evaluated statistically using logistic regression analysis. The NFKB1 -94 polymorphism was shown to decrease prostate cancer risk in both heterozygous and homozygous comparison models (odds ratios of 0.74 (95% CI = 0.58-0.96) (P = 0.02) and 0.57 (95% CI = 0.42-0.78) (P < 0.01), resp.). An opposite finding was observed for COX-2 (-1195) polymorphism (odds ratios of 1.58 (95% CI = 1.15-2.18) (P < 0.01) for heterozygous comparison model and 2.08 (95% CI = 1.48-2.92) (P < 0.01) for homozygous comparison model). No association was observed for other polymorphisms. In conclusion, NFKB1 -94 ins/del and COX-2 (-1195G>A) polymorphisms may be, respectively, associated with decreased and increased prostate cancer risk in the Chinese population.

The development of the B-lymphoid cell lineage is tightly controlled by the concerted action of a network of transcriptional and epigenetic regulators. EBF1, a central component of this network, is essential for B-lymphoid specification and commitment as well as for the maintenance of the B-cell identity. Genetic alterations causing loss of function of these B-lymphopoiesis regulators have been implicated in the pathogenesis of B-lymphoid malignancies, with particular regard to B-cell acute lymphoblastic leukaemias (B-ALLs), where their presence is frequently detected. The activity of the B-cell regulatory network may also be disrupted by the aberrant expression of inhibitory molecules. In particular, two multi-zinc finger transcription cofactors named ZNF423 and ZNF521 have been characterised as potent inhibitors of EBF1 and are emerging as potentially relevant contributors to the development of B-cell leukaemias. Here we will briefly review the current knowledge of these factors and discuss the importance of their functional cross talk with EBF1 in the development of B-cell malignancies.