Role of microRNAs in regulation of doxorubicin and paclitaxel responses in lung tumor cells

Abstract Lung cancer as the leading cause of cancer related mortality is always one of the main global health challenges. Despite the recent progresses in therapeutic methods, the mortality rate is still significantly high among lung cancer patients. A wide range of therapeutic methods including chemotherapy, radiotherapy, and surgery are used to treat lung cancer. Doxorubicin (DOX) and Paclitaxel (TXL) are widely used as the first-line chemotherapeutic drugs in lung cancer. However, there is a significant high percentage of DOX/TXL resistance in lung cancer patients, which leads to tumor recurrence and metastasis. Considering, the side effects of these drugs in normal tissues, it is required to clarify the molecular mechanisms of DOX/TXL resistance to introduce the efficient prognostic and therapeutic markers in lung cancer. MicroRNAs (miRNAs) have key roles in regulation of different pathophysiological processes including cell division, apoptosis, migration, and drug resistance. MiRNA deregulations are widely associated with chemo resistance in various cancers. Therefore, considering the importance of miRNAs in chemotherapy response, in the present review, we discussed the role of miRNAs in regulation of DOX/TXL response in lung cancer patients. It has been reported that miRNAs mainly induced DOX/TXL sensitivity in lung tumor cells by the regulation of signaling pathways, autophagy, transcription factors, and apoptosis. This review can be an effective step in introducing miRNAs as the non-invasive prognostic markers to predict DOX/TXL response in lung cancer patients

PI3K/AKT signaling pathway as a critical regulator of epithelial-mesenchymal transition in colorectal tumor cells

Abstract Colorectal cancer (CRC) is one of the most frequent gastrointestinal malignancies that are considered as a global health challenge. Despite many progresses in therapeutic methods, there is still a high rate of mortality rate among CRC patients that is associated with poor prognosis and distant metastasis. Therefore, investigating the molecular mechanisms involved in CRC metastasis can improve the prognosis. Epithelial-mesenchymal transition (EMT) process is considered as one of the main molecular mechanisms involved in CRC metastasis, which can be regulated by various signaling pathways. PI3K/AKT signaling pathway has a key role in CRC cell proliferation and migration. In the present review, we discussed the role of PI3K/AKT pathway CRC metastasis through the regulation of the EMT process. It has been shown that PI3K/AKT pathway can induce the EMT process by down regulation of epithelial markers, while up regulation of mesenchymal markers and EMT-specific transcription factors that promote CRC metastasis. This review can be an effective step toward introducing the PI3K/AKT/EMT axis to predict prognosis as well as a therapeutic target among CRC patients. Video Abstrac

Long non-coding RNAs as the critical regulators of PI3K/AKT, TGF-β, and MAPK signaling pathways during breast tumor progression

Abstract Breast cancer (BC) as one of the most common causes of human deaths among women, is always considered one of the global health challenges. Despite various advances in diagnostic and therapeutic methods, a significant percentage of BC patients have a poor prognosis due to the lack of therapeutic response. Therefore, investigating the molecular mechanisms involved in BC progression can improve the therapeutic and diagnostic strategies in these patients. Cytokine and growth factor-dependent signaling pathways play a key role during BC progression. In addition to cytokines and growth factors, long non-coding RNAs (lncRNAs) have also important roles in regulation of such signaling pathways. Therefore, in the present review we discussed the role of lncRNAs in regulation of PI3K/AKT, MAPK, and TGF-β signaling pathways in breast tumor cells. It has been shown that lncRNAs mainly have an oncogenic role through the promotion of these signaling pathways in BC. This review can be an effective step in introducing the lncRNAs inhibition as a probable therapeutic strategy to reduce tumor growth by suppression of PI3K/AKT, MAPK, and TGF-β signaling pathways in BC patients. In addition, considering the oncogenic role and increased levels of lncRNAs expressions in majority of the breast tumors, lncRNAs can be also considered as the reliable diagnostic markers in BC patients

MicroRNAs as the critical regulators of autophagy-mediated cisplatin response in tumor cells

Abstract Chemotherapy is one of the most common therapeutic methods in advanced and metastatic tumors. Cisplatin (CDDP) is considered as one of the main first-line chemotherapy drugs in solid tumors. However, there is a high rate of CDDP resistance in cancer patients. Multi-drug resistance (MDR) as one of the main therapeutic challenges in cancer patients is associated with various cellular processes such as drug efflux, DNA repair, and autophagy. Autophagy is a cellular mechanism that protects the tumor cells toward the chemotherapeutic drugs. Therefore, autophagy regulatory factors can increase or decrease the chemotherapy response in tumor cells. MicroRNAs (miRNAs) have a pivotal role in regulation of autophagy in normal and tumor cells. Therefore, in the present review, we discussed the role of miRNAs in CDDP response through the regulation of autophagy. It has been reported that miRNAs mainly increased the CDDP sensitivity in tumor cells by inhibition of autophagy. PI3K/AKT signaling pathway and autophagy-related genes (ATGs) were the main targets of miRNAs in the regulation of autophagy-mediated CDDP response in tumor cells. This review can be an effective step to introduce the miRNAs as efficient therapeutic options to increase autophagy-mediated CDDP sensitivity in tumor cells

Role of the long non-coding RNAs in regulation of Gemcitabine response in tumor cells

Abstract Chemotherapy is widely used as one of the first line therapeutic methods in cancer patients. However, chemotherapeutic resistance is one of the most common problems in cancer patients, which leads to the therapeutic failure and tumor relapse. Considering the side effects of chemotherapy drugs in normal tissues, it is required to investigate the molecular mechanisms involved in drug resistance to improve the therapeutic strategies in cancer patients. Long non-coding RNAs (lncRNAs) have pivotal roles in regulation of cellular processes associated with drug resistance. LncRNAs deregulations have been frequently reported in a wide range of chemo-resistant tumors. Gemcitabine (GEM) as a nucleoside analog has a wide therapeutic application in different cancers. However, GEM resistance is considered as a therapeutic challenge. Considering the role of lncRNAs in the occurrence of GEM resistance, in the present review we discussed the molecular mechanisms of lncRNAs in regulation of GEM response among cancer patients. It has been reported that lncRNAs have mainly an oncogenic role as the inducers of GEM resistance through direct or indirect regulation of transcription factors, autophagy, polycomb complex, and signaling pathways such as PI3K/AKT, MAPK, WNT, JAK/STAT, and TGF-β. This review paves the way to present the lncRNAs as non-invasive markers to predict GEM response in cancer patients. Therefore, lncRNAs can be introduced as the efficient markers to reduce the possible chemotherapeutic side effects in GEM resistant cancer patients and define a suitable therapeutic strategy among these patients

PRC2 mediated KLF2 down regulation: a therapeutic and diagnostic axis during tumor progression

Abstract Surgery and chemo-radiotherapy are used as the common first-line treatment options in many cancers. However, tumor relapse is observed in many cancer patients following such first-line treatments. Therefore, targeted therapy according to the molecular cancer biology can be very important in reducing tumor recurrence. In this regard, a wide range of monoclonal antibodies against the growth factors and their receptors can offer more targeted treatment in cancer patients. However, due to the importance of growth factors in the normal biology of body cells, side effects can also be observed following the application of growth factor inhibitors. Therefore, more specific factors should be introduced as therapeutic targets with less side effects. Krüppel-like factors 2 (KLF2) belongs to the KLF family of transcription factors that are involved in the regulation of many cellular processes. KLF2 deregulations have been also reported during the progression of many tumors. In the present review we discussed the molecular mechanisms of KLF2 during tumor growth and invasion. It has been shown that the KLF2 as a tumor suppressor is mainly inhibited by the non-coding RNAs (ncRNAs) through the polycomb repressive complex 2 (PRC2) recruitment. This review is an effective step towards introducing the KLF2 as a suitable diagnostic and therapeutic target in cancer patients

MicroRNAs as the pivotal regulators of cisplatin resistance in head and neck cancers

Abstract Although, there is a high rate of good prognosis in early stage head and neck tumors, about half of these tumors are detected in advanced stages with poor prognosis. A combination of chemotherapy, radiotherapy, and surgery is the treatment option in head and neck cancer (HNC) patients. Although, cisplatin (CDDP) as the first-line drug has a significant role in the treatment of HNC patients, CDDP resistance can be observed in a large number of these patients. Therefore, identification of the molecular mechanisms involved in CDDP resistance can help to reduce the side effects and also provides a better therapeutic management. MicroRNAs (miRNAs) as the post-transcriptional regulators play an important role in drug resistance. Therefore, in the present review we investigated the role of miRNAs in CDDP response of head and neck tumors. It has been reported that the miRNAs exerted their roles in CDDP response by regulation of signaling pathways such as WNT, NOTCH, PI3K/AKT, TGF-β, and NF-kB as well as apoptosis, autophagy, and EMT process. The present review paves the way to suggest a non-invasive miRNA based panel marker for the prediction of CDDP response among HNC patients. Therefore, such diagnostic miRNA based panel marker reduces the CDDP side effects and improves the clinical outcomes of these patients following an efficient therapeutic management

The therapeutic potential value of Cancer-testis antigens in immunotherapy of gastric cancer

Gastric cancer (GC) is the fourth most common cause of mortality and the fifth for incidence, globally. Diagnosis, early prognosis, and therapy remains challenging for this condition, and new tumor-associated antigens are required for its detection and immunotherapy. Cancer-testis antigens (CTAs) are a subfamily of tumor-associated antigens (TAAs) that have been identified as potential biomarkers and targets for cancer immunotherapy. The CTAs-restricted expression pattern in tumor cells and their potential immunogenicity identify them as attractive target candidates in CTA-based diagnosis or prognosis or immunotherapy. To date, numerous studies have reported the dysregulation of CTAs in GC. Several clinical trials have been done to assess CTA-based immunotherapeutic potential in the treatment of GC patients. NY-ESO-1, MAGE, and KK-LC-1 have been used in GC clinical trials. We review recent studies that have investigated the potential of the CTAs in GC regarding the expression, function, aggressive phenotype, prognosis, and immunological responses as well as their possible clinical significance as immunotherapeutic targets with a focus on challenges and future interventions