Long non-coding RNAs in the doxorubicin resistance of cancer cells.

Chemotherapy is the main treatment used for cancer patients failing surgery. Doxorubicin (DOX) is a well-known chemotherapeutic agent capable of suppressing proliferation in cancer cells and triggering apoptosis via inhibiting topoisomerase II activity and producing DNA breaks. This activity of DOX restrains mitosis and cell cycle progression. However, frequent application of DOX results in the emergence of resistance in the cancer cells. It seems that genetic and epigenetic factors can provide DOX resistance of cancer cells. Long non-coding RNAs (lncRNAs) are a subcategory of non-coding RNAs with role in the regulation of several cellular processes such as proliferation, migration, differentiation and apoptosis. LncRNA dysregulation has been associated with chemoresistance, and this profile occurs upon DOX treatment of cancer. In the present review, we focus on the role of lncRNAs in mediating DOX resistance and discuss the molecular pathways and mechanisms. LncRNAs can drive DOX resistance via activating pathways such as NF-κB, PI3K/Akt, Wnt, and FOXC2. Some lncRNAs can activate protective autophagy in response to the stress caused by DOX, which mediates resistance. In contrast, there are other lncRNAs involved in the sensitivity of cancer cells to DOX, such as GAS5, PTCSC3 and FENDRR. Some anti-tumor agents such as polydatin can regulate the expression of lncRNAs, enhancing DOX sensitivity. Overall, lncRNAs are potential players in DOX resistance, and their identification and targeting are of importance in chemosensitivity. Furthermore, these findings can be translated into clinical for treatment of cancer patients.

The role of SOX family transcription factors in gastric cancer.

Gastric cancer (GC) is a leading cause of death worldwide. GC is the third-most common cause of cancer-related death after lung and colorectal cancer. It is also the fifth-most commonly diagnosed cancer. Accumulating evidence has revealed the role of signaling networks in GC progression. Identification of these molecular pathways can provide new insight into therapeutic approaches for GC. Several molecular factors involved in GC can play both onco-suppressor and oncogene roles. Sex-determining region Y (Sry)-box-containing (SOX) family members are transcription factors with a well-known role in cancer. SOX proteins can bind to DNA to regulate cellular pathways via a highly conserved domain known as high mobility group (HMG). In the present review, the roles of SOX proteins in the progression and/or inhibition of GC are discussed. The dual role of SOX proteins as tumor-promoting and tumor-suppressing factors is highlighted. SOX members can affect upstream mediators (microRNAs, long non-coding RNAs and NF-κB) and down-stream mediators (FAK, HIF-1α, CDX2 and PTEN) in GC. The possible role of anti-tumor compounds to target SOX pathway members in GC therapy is described. Moreover, SOX proteins may be used as diagnostic or prognostic biomarkers in GC.