MicroRNAs play an important role in the regulation of cancer migration, invasion and metastasis. Patients with triple-negative breast cancer (TNBC) have a high incidence of early relapse and metastasis; however, the molecular basis for metastasis and recurrence in these individuals remains largely unknown. Herein, we demonstrate that miR-136 is an anti-invasive microRNA in TNBC and suppresses mesenchymal invasion and metastasis. Our results demonstrated that miR-136 was downregulated in TNBC and negative correlated with the WHO grades. However, RASAL2 was identified as a functional target of miR-136, and was overexpressed in TNBC and correlates with pathological grades. Moreover, overexpression of RASAL2 in a breast cancer cell line rescued miR-136-mediated cell migration and invasion. In conclusion, these results indicate that the miR-136/RASAL2/MET axis act as a suppressor of TNBC metastasis.

H19, a paternally imprinted noncoding RNA, has been found to be overexpressed in various cancers, including colorectal cancer (CRC), and may function as an oncogene. However, the mechanism by which H19 regulates CRC progression remains poorly understood. In this study, we aimed to assess H19 expression levels in CRC tissues, determine the effect of H19 on CRC proliferation, and explore the mechanism by which H19 regulates the proliferation of CRC. We measured H19 expression using qRT-PCR and analysed the effects of H19 on colon cancer cell proliferation via cell growth curve, cell viability assay, and colony formation assays. To elucidate the mechanism underlying these effects, we analysed the interactions between H19 and miRNAs and identified the target gene to which H19 and miRNA competitively bind using a series of molecular biological techniques. H19 expression was upregulated in CRC tissues compared with adjacent noncancerous tissues. H19 overexpression facilitated colon cancer cell proliferation, whereas H19 knockdown inhibited cell proliferation. miR-200a bound to H19 and inhibited its expression, thereby decreasing CRC cell proliferation. β-Catenin was identified as a target gene of miR-200a. H19 regulated β-catenin expression and activity by competitively binding to miR-200a. H19 promotes cell proliferation by competitively binding to miR-200a and derepressing β-catenin in CRC.

The DNA damage response (DDR) is one of the most important mechanisms of platinum resistance in ovarian cancer. Some miRNAs have been identified to be involved in the regulatory network of DDR, thus the abnormal expression of miRNAs might affect platinum chemosensitivity in ovarian cancer. In this study, by assessing miRNAs simultaneously targeting a set of DDR genes that exhibited response to platinum, we found that miR-211 inhibited most of those genes, and proposed that miR-211 might affect the sensitivity of ovarian cancer cells to platinum by targeting multiple DDR genes and thereby determine the prognosis of ovarian cancer. To verify the hypothesis, we analyzed the association between miR-211 level and clinical prognosis, assessed the effect of miR-211 on DDR and platinum chemosensitivity, and explored the possible molecular mechanism. We revealed that miR-211 enhanced platinum chemosensitivity and was positively correlated with favorable outcomes in ovarian cancer patients. Many DDR genes including TDP1 were identified as targets of miR-211. In contrast, TDP1 suppressed DNA damage and platinum chemosensitivity. Moreover, the miR-211 level in tissues was shown to be associated with the good outcome of neoadjuvant chemotherapy and negatively correlated with the expression of TDP1. Conclusively, we demonstrated that miR-211 improves the prognosis of ovarian cancer patients by enhancing the chemosensitivity of cancer cells to platinum via inhibiting DDR gene expression, which provides an essential basis to identify novel treatment targets to block DDR effectively and improve chemosensitivity in ovarian cancer.

Background: It has been widely accepted that hepatitis B virus X protein (HBx) plays an important role in hepatocellular carcinoma (HCC). This study aimed to explore the function of long non-coding RNAs (lncRNAs) in the epithelial-mesenchymal transition (EMT) induced by HBx. Methods: The association between HBx and EMT markers was detected using immunohistochemistry in HCC tissues. The effect of HBx on HCC EMT was assessed through morphological analysis, transwell assay, metastatic in vivo study and detection of EMT markers. LncRNA microarray was used to screen the differently expressed lncRNAs. Small interfering RNA and Western blot were used to analyse the function and mechanism of the locked lncRNA. Results: HBx was negatively correlated with the epithelial marker E-cadherin but positively correlated with the mesenchymal marker vimentin in HCC tissues. HBx induced the mesenchymal phenotype and improved the metastatic ability of HCC cells. Meanwhile, HBx down-regulated E-cadherin, whereas it up-regulated vimentin. In HCC cells, HBx altered the expression of 2002 lncRNAs by more than 2-fold. One of them was ZEB2-AS1. Inhibition of ZEB2-AS1 can compensate for the EMT phenotype and reverse the expression of EMT markers regulated by HBx. Additionally, HBx affected the Wnt signalling pathway. Conclusions: HBx promotes HCC cell metastasis by inducing EMT, which is at least partly mediated by lncRNAs.

Ovarian cancer is often accompanied by the production of ascites, and patients with repeated ascites are associated with chemotherapy resistance. The previous study confirmed that the ovarian cancer patients who developed ascites after chemotherapy had elevated autophagy levels in the ascites and precipitated cells, which was positively correlated with MDR1 expression in the blood of patients. In order to explore the correlation between autophagy and chemoresistant, we searched TCGA and GEO database to analyze the correlation between LC3B and MDR1, and identified the targeting miRNA of LC3B. It was verified by dual luciferase that miR-204 can target LC3B. The ovarian cancer cell line and the BALB/c nude mice tumor-bearing model were selected for in vitro and in vivo verification. In vitro studies confirmed that ovarian cancer cells were more sensitive to cisplatin by inhibiting LC3B. Overexpression of miR-204 reduced the expression of LC3B, Atg7, and MDR1, and promoted apoptosis. In vivo studies have also confirmed that reducing the level of autophagy in ovarian cancer cells increases the sensitivity to cisplatin. It suggests that miR-204 can be used as a tumor suppressor gene and LC3B expression level can be used as a potential molecular marker to guide the diagnosis and treatment of patients with ovarian cancer.

: As the major and preferred treatment for ovarian cancer ascites, chemotherapy can reduce or inhibit recurrent ascites (hereafter re-ascites); however, some patients still experience re-ascites. Therefore, this study investigated cases in which epithelial ovarian cancer (EOC) patients experienced re-ascites. In re-ascites cases, CA125, MDR1, LC-3, and Beclin-1 were highly expressed. In addition, CASP-9 and c-CASP-3 expression levels were decreased, and serum CA125 levels (highest 4348 U/ml) were increased compared to chemosensitive cases. The results suggest that high expression levels of Beclin-1 and LC-3, thus increasing the level of autophagy and inhibiting apoptosis in the no-chemotherapy group. In the chemosensitive group, survivin expression was decreased and CASP-9 expression was increased, which led to c-CASP-3 activation and increased tumor cell apoptosis. The results of the cell lines confirm that inhibition of autophagy can increase the sensitivity of ovarian cancer cells to CDDP and promote CDDP-induced cell death. Re-ascites, which appears after chemotherapy, may be associated with drug resistance. In addition, increased autophagy may protect tumor cells from chemotherapeutic drugs, thus inhibiting tumor cell death.