MiR-138: A promising therapeutic target for cancer.

MicroRNAs are small noncoding RNAs which regulate gene expressions at post-transcriptional level by binding to the 3'-untranslated region of target messenger RNAs. Growing evidences highlight their pivotal roles in various biological processes of human cancers. Among them, miR-138, generating from two primary transcripts, pri-miR-138-1 and pri-miR-138-2, expresses aberrantly in different cancers and is extensively studied in cancer network. Importantly, studies have shown that miR-138 acts as a tumor suppressor by targeting many target genes, which are related to proliferation, apoptosis, invasion, and migration. Additionally, some researches also discover that miR-138 can sensitize tumors to chemotherapies. In this review, we summarize the expression of miR-138 on regulatory mechanisms and tumor biological processes, which will establish molecular basis on the usage of miR-138 in clinical applications in the future.

WITHDRAWN: The long non-coding RNA, LINC00635-001, sensitizes EGFR-TKI-resistant human lung cancer cells in vitro by inhibiting Akt activation.

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Liver X receptor as a drug target for the treatment of breast cancer.

Liver X receptor (LXR) has been exploited widely as a drug target in breast cancer treatment, and various mechanisms underlying the effects of LXR in this area are well studied. The activated LXR plays important roles in estrogen receptor α (ERα) breast cancer cells, such as reducing cell proliferation and arresting cell cycle progression. Different LXR ligands have diverse effects on the development of breast cancer, such as the inhibitory effect of oxysterol, which can return cells to normocholesterol conditions and target other metabolic genes. Moreover, 27-hydroxycholesterol, a locally produced cholesterol metabolite, reportedly promotes the proliferation of ERα breast cancer cells in vitro and facilitates tumor metastasis with other LXR ligands. Moreover, the expression of LXR also exerts potential effects on immune surveillance, tumor immunity, and tumor microenvironment. These advances in breast cancer research indicate that LXR may be a new therapeutic target to treat the refractory or drug-resistant subtypes of breast cancer.

DNA methylation mediated silencing of microRNA-874 is a promising diagnosis and prognostic marker in breast cancer.

MicroRNA-874 (miR-874) is downregulated in several human cancers and has been suggested to be a tumor suppressor gene. However, the molecular mechanism of miR-874 downregulation in breast cancer has not been well elucidated. Here we aimed to study the aberrant hyper-methylation of CpG sites with the utility of miR-874 downreregulation in breast cancer and evaluate the clinical function of miR-874 as a prognostic marker. The miR-874 expressions in cells and tissues of two breast cancer lines were measured by real-time PCR. The DNA methylation status of the miR-874 promoter region in 19 pairs of breast cancer and adjacent normal samples was analyzed with Sequenom EpiTYPER MassArray. To evaluate whether miR-874 is a potential prognostic marker in breast cancer, we also explored the clinical long-time follow-up records from The Cancer Genome Atlas (TCGA). We found miR-874 expression was downregulated in 47 pairs of breast cancer tissues. Moreover, univariate and multivariate analysis revealed miR-874 expression may be a prognostic biomarker of overall survival in breast cancer patients. Preconditioning with 5-Aza-CdR in two cell lines elevated miR-874 expressions. The data from Sequenom EpiTYPER MassArray showed that DNA methylation of the promoter region of miR-874 was upregulated and accompanied by decreased miR-874 expression, which was further confirmed by TCGA. After comprehensive considerations, we think miR-874, which might be served as a prognostic biomarker, is mediated by DNA methylation.

Chimaeric antigen receptor T-cell therapy for tumour immunotherapy.

Chimaeric antigen receptor (CAR) T-cell therapies, as one of the cancer immunotherapies, have heralded a new era of treating cancer. The accumulating data, especially about CAR-modified T cells against CD19 support that CAR T-cell therapy is a highly effective immune therapy for B-cell malignancies. Apart from CD19, there have been many trials of CAR T cells directed other tumour specific or associated antigens (TSAs/TAAs) in haematologic malignancies and solid tumours. This review will briefly summarize basic CAR structure, parts of reported TSAs/TAAs, results of the clinical trials of CAR T-cell therapies as well as two life-threatening side effects. Experiments in vivo or in vitro, ongoing clinical trials and the outlook for CAR T-cell therapies also be included. Our future efforts will focus on identification of more viable cancer targets and more strategies to make CAR T-cell therapy safer.

MiR-31 inhibits migration and invasion by targeting SATB2 in triple negative breast cancer.

Metastasis is the leading cause of death among breast cancer (BCa) patients and triple negative breast cancer (TNBC) as one of BCa subtypes exhibits the worst survival rate due to its highly aggressive and metastatic behavior. A growing body of research has shown that the dynamic expression of microRNAs (miRNAs) was intimately associated with tumor invasion and metastasis. Recent studies have demonstrated miR-31 as a metastasis-suppressor in breast cancer, but it is still known little about the mechanism of it suppresses metastasis. The special AT-rich sequence-binding protein-2 (SATB2) has been reported to involve in tumor proliferation and invasion, but its function and relationship with miR-31 in breast cancer is still unknown. Here we found that the expression of miR-31 was downregulated in TNBC tissue and cell line. MiR-31 expression was increased after MDA-MB-231 cell was treated by 5-aza-2'-deoxycytidine (5-AZA-CdR), enhance the expression of miR-31 significantly inhibited MDA-MB-231 cell migration and invasion, downregulation of miR-31 expression could promoted MCF-7 cell migration and invasion. The expression of SATB2 was negatively correlated with miR-31 and was upregulated in MCF-7 and MDA-MB-231. Silencing SATB2 expression significantly inhibited MCF-7 and MDA-MB-231 cell proliferation, migration and invasion. Luciferase reporter assays indicated SATB2 is a direct target of miR-31. Taken together, these results suggest miR-31 inhibited TNBC cells migration and invasion through suppressing SATB2 expression.