Epigenetic regulation of hepatocellular carcinoma progression: MicroRNAs as therapeutic, diagnostic and prognostic factors.

Hepatocellular carcinoma (HCC), a significant challenge for public healthcare systems in developed Western countries including the USA, Canada, and the UK, is influenced by different risk factors including hepatitis virus infections, alcoholism, and smoking. The disruption in the balance of microRNAs (miRNAs) plays a vital function in tumorigenesis, given their function as regulators in numerous signaling networks. These miRNAs, which are mature and active in the cytoplasm, work by reducing the expression of target genes through their impact on mRNAs. MiRNAs are particularly significant in HCC as they regulate key aspects of the tumor, like proliferation and invasion. Additionally, during treatment phases such as chemotherapy and radiotherapy, the levels of miRNAs are key determinants. Pre-clinical experiments have demonstrated that altered miRNA expression contributes to HCC development, metastasis, drug resistance, and radio-resistance, highlighting related molecular pathways and processes like MMPs, EMT, apoptosis, and autophagy. Furthermore, the regulatory role of miRNAs in HCC extends beyond their immediate function, as they are also influenced by other epigenetic factors like lncRNAs and circular RNAs (circRNAs), as discussed in recent reviews. Applying these discoveries in predicting the prognosis of HCC could mark a significant advancement in the therapy of this disease.

Towards dual function of autophagy in breast cancer: A potent regulator of tumor progression and therapy response.

As a devastating disease, breast cancer has been responsible for decrease in life expectancy of females and its morbidity and mortality are high. Breast cancer is the most common tumor in females and its treatment has been based on employment of surgical resection, chemotherapy and radiotherapy. The changes in biological behavior of breast tumor relies on genomic and epigenetic mutations and depletions as well as dysregulation of molecular mechanisms that autophagy is among them. Autophagy function can be oncogenic in increasing tumorigenesis, and when it has pro-death function, it causes reduction in viability of tumor cells. The carcinogenic function of autophagy in breast tumor is an impediment towards effective therapy of patients, as it can cause drug resistance and radio-resistance. The important hallmarks of breast tumor such as glucose metabolism, proliferation, apoptosis and metastasis can be regulated by autophagy. Oncogenic autophagy can inhibit apoptosis, while it promotes stemness of breast tumor. Moreover, autophagy demonstrates interaction with tumor microenvironment components such as macrophages and its level can be regulated by anti-tumor compounds in breast tumor therapy. The reasons of considering autophagy in breast cancer therapy is its pleiotropic function, dual role (pro-survival and pro-death) and crosstalk with important molecular mechanisms such as apoptosis. Moreover, current review provides a pre-clinical and clinical evaluation of autophagy in breast tumor.

Biological functions and molecular interactions of Wnt/ß-catenin in breast cancer: Revisiting signaling networks.

Changes in lifestyle such as physical activity and eating habits have been one of the main reasons for development of various diseases in modern world, especially cancer. However, role of genetic factors in initiation of cancer cannot be ignored and Wnt/ß-catenin signaling is such factor that can affect tumor progression. Breast tumor is the most malignant tumor in females and it causes high mortality and morbidity around the world. The survival and prognosis of patients are not still desirable, although there have been advances in introducing new kinds of therapies and diagnosis. The present review provides an update of Wnt/ß-catenin function in breast cancer malignancy. The upregulation of Wnt is commonly observed during progression of breast tumor and confirms that tumor cells are dependent on this pathway Wnt/ß-catenin induction prevents apoptosis that is of importance for mediating drug resistance. Furthermore, Wnt/ß-catenin signaling induces DNA damage repair in ameliorating radio-resistance. Wnt/ß-catenin enhances proliferation and metastasis of breast tumor. Wnt/ß-catenin induces EMT and elevates MMP expression. Furthermore, Wnt/ß-catenin participates in tumor microenvironment remodeling and due to its tumor-promoting factor, drugs for its suppression have been developed. Different kinds of upstream mediators Wnt/ß-catenin signaling in breast cancer have been recognized that their targeting is a therapeutic approach. Finally, Wnt/ß-catenin can be considered as a biomarker in clinical trials.

Long non-coding RNAs (lncRNAs) in hepatocellular carcinoma progression: Biological functions and new therapeutic targets.

Liver is an important organ in body that performs vital functions such as detoxification. Liver is susceptible to development of cancers, and hepatocellular carcinoma (HCC) is among them. 75-85% of liver cancer cases are related to HCC. Therefore, much attention has been directed towards understanding factors mediating HCC progression. LncRNAs are epigenetic factors with more than 200 nucleotides in length located in both nucleus and cytoplasm and they are promising candidates in cancer therapy. Directing studies towards understanding function of lncRNAs in HCC is of importance. LncRNAs regulate cell cycle progression and growth of HCC cells, and they can also induce/inhibit apoptosis in tumor cells. LncRNAs affect invasion and metastasis in HCC mainly by epithelial-mesenchymal transition (EMT) mechanism. Revealing the association between lncRNAs and downstream signaling pathways in HCC is discussed in the current manuscript. Infectious diseases can affect lncRNA expression in mediating HCC development and then, altered expression level of lncRNA is associated with drug resistance and radio-resistance. Biomarker application of lncRNAs and their role in prognosis and diagnosis of HCC are also discussed to pave the way for treatment of HCC patients.