Role of microRNA-505 during tumor progression and metastasis.

Late diagnosis of cancer in advanced stages due to the lack of screening methods is considered as the main cause of poor prognosis and high mortality rate among these patients. Therefore, it is necessary to investigate the molecular tumor biology in order to introduce biomarkers that can be used in cancer screening programs and early diagnosis. MicroRNAs (miRNAs) have key roles in regulation of the cellular pathophysiological processes. Due to the high stability of miRNAs in body fluids, they are widely used as the non-invasive tumor markers. According to the numerous reports about miR-505 deregulation in a wide range of cancers, we investigated the role of miR-505 during tumor progression. It was shown that miR-505 mainly has the tumor suppressor functions through the regulation of signaling pathways, chromatin remodeling, and cellular metabolism. This review has an effective role in introducing miR-505 as a suitable marker for the early cancer diagnosis.

Role of microRNAs in tumor progression by regulation of kinesin motor proteins.

Aberrant cell proliferation is one of the main characteristics of tumor cells that can be affected by many cellular processes and signaling pathways. Kinesin superfamily proteins (KIFs) are motor proteins that are involved in cytoplasmic transportations and chromosomal segregation during cell proliferation. Therefore, regulation of the KIF functions as vital factors in chromosomal stability is necessary to maintain normal cellular homeostasis and proliferation. KIF deregulations have been reported in various cancers. MicroRNAs (miRNAs) and signaling pathways are important regulators of KIF proteins. MiRNAs have key roles in regulation of the cell proliferation, migration, and apoptosis. In the present review, we discussed the role of miRNAs in tumor biology through the regulation of KIF proteins. It has been shown that miRNAs have mainly a tumor suppressor function via the KIF targeting. This review can be an effective step to introduce the miRNAs/KIFs axis as a probable therapeutic target in tumor cells.

Role of microRNA-494 in tumor progression.

Various progresses in tumor therapy during the recent decades have significantly reduced the cancer related deaths globally. However, there is still a high rate of mortality in these patients. The early stage tumors have no aggressive and clear clinical symptoms in the majority of cancer types, which causes a high rate of therapeutic failure in advanced tumor stages. Therefore, identification of the molecular tumor biology can be promising to introduce the early diagnostic markers. MicroRNAs (miRNAs) are the key regulators of cellular processes that can also be involved in tumor progression as tumor-suppressor or oncogene. Due to the high stability of miRNAs in body fluids, they can be used as the non-invasive diagnostic tumor markers. In the present review, we discussed the role of miR-494 in tumor progression. It has been shown that miR-494 has mainly a tumor suppressor function by regulation of transcriptional and structural factors and signaling pathways such as transforming growth factor-ß (TGF-ß), WNT, and Janus kinase (JAK)-signal transducer and activator of transcription (STAT). The phosphatase and tensin homolog/phosphoinositide 3-kinase (PTEN/PI3K) axis has been also reported as the main target of miR-494 as an oncogene. These findings suggest that miR-494 is a non-invasive diagnostic marker for the early diagnosis and therapeutic management of cancer patients.

MicroRNAs as the critical regulators of tumor angiogenesis in liver cancer.

Liver cancer is one of the most common malignancies in human digestive system. Despite the recent therapeutic methods, there is a high rate of mortality among liver cancer patients. Late diagnosis in the advanced tumor stages can be one of the main reasons for the poor prognosis in these patients. Therefore, investigating the molecular mechanisms of liver cancer can be helpful for the early stage tumor detection and treatment. Vascular expansion in liver tumors can be one of the important reasons for poor prognosis and aggressiveness. Therefore, anti-angiogenic drugs are widely used in liver cancer patients. MicroRNAs (miRNAs) have key roles in the regulation of angiogenesis in liver tumors. Due to the high stability of miRNAs in body fluids, these factors are widely used as the non-invasive diagnostic and prognostic markers in cancer patients. Regarding, the importance of angiogenesis during liver tumor growth and invasion, in the present review, we discussed the role of miRNAs in regulation of angiogenesis in these tumors. It has been reported that miRNAs mainly exert an anti-angiogenic function by regulation of tumor microenvironment, transcription factors, and signaling pathways in liver tumors. This review can be an effective step to suggest the miRNAs for the non-invasive early detection of malignant and invasive liver tumors.

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

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.

MicroRNA-495: a therapeutic and diagnostic tumor marker.

Therapeutic and diagnostic progresses have significantly reduced the mortality rate among cancer patients during the last decade. However, there is still a high rate of mortality among cancer patients. One of the important reasons involved in the high mortality rate is the late diagnosis in advanced tumor stages that causes the failure of therapeutic strategies in these patients. Therefore, investigating the molecular mechanisms involved in tumor progression has an important role in introducing the efficient early detection markers. MicroRNAs (miRNAs) as stable factors in body fluids are always considered as non-invasive diagnostic and prognostic markers. In the present review, we investigated the role of miR-495 in tumor progression. It has been reported that miR-495 has mainly a tumor suppressor function through the regulation of transcription factors and tyrosine kinases as well as cellular processes such as multidrug resistance, chromatin remodeling, and signaling pathways. This review can be an effective step towards introducing the miR-495 as a non-invasive diagnostic/prognostic marker as well as a suitable target in tumor therapy.

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

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-ß, 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.

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

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-ß 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-ß 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.

Plasma microRNA-195, -34c, and - 1246 as novel biomarkers for the diagnosis of trastuzumab-resistant HER2-positive breast cancer patients.

Recently, miRNAs have been regarded as potential candidates for mediating therapeutic functions by targeting genes related to drug response. In this study, we suggested that plasma miRNAs may be correlated with response to trastuzumab in HER2-positive breast cancer patients. To determine whether miR-195, miR-23b-3p, miR-1246, and miR-34c-3p are involved in trastuzumab resistance, we screened their expressions in the BT-474 cell line, which was followed by plasma analysis from 20 trastuzumab-resistant HER2-positive breast cancer patients and 20 nonresistance subjects. Then, TargetScan, Pictar, and miRDB were applied to find the possible targets of the selected miRNAs. In addition, the expression status of admitted targets was evaluated. Our results showed that in resistant BT-474 cells, miR-1246, and miR-23b-3p were significantly upregulated, and miR-195-5p and miR-34c-3p were downregulated. In plasma analysis, we found miR-195-5p, miR-34c-3p, and miR-1246 meaningfully diminished in the resistant group, while the expression of miR-23b-3p was not statistically different. The expression levels of confirmed targets by qRT-PCR showed that the expression of RAF1, AKT3, c-MET, CCND1, PHLPP2, MYB, MAP2K1, and PTEN was significantly upregulated, while the expression of CCNG2 was significantly downregulated. The networks of miRNAs with their confirmed targets improved comprehension of miRNA-mediated therapeutic responses to trastuzumab and might be proposed for more characterization of miRNA functions. Moreover, these data indicated that miR-195-5p, miR-34c-3p, and miR-1246 could be possible biomarkers for prognosis and early detection of the trastuzumab-resistant group from the sensitive group of HER2-positive breast cancer patients.

Forkhead box proteins as the critical regulators of cisplatin response in tumor cells.

Cisplatin (CDDP) is one of the most common chemotherapy drugs used in a wide range of cancer patients; however, there is a high rate of CDDP resistance among cancer patients. Considering the side effects of cisplatin in normal tissues, it is necessary to predict the CDDP response in cancer patients. Therefore, identifying the molecular mechanisms involved in CDDP resistance can help to introduce the prognostic markers. Several molecular mechanisms such as apoptosis inhibition, drug efflux, drug detoxification, and increased DNA repair are involved in CDDP resistance. Regarding the key role of transcription factors in regulation of many cellular processes related to drug resistance, in the present review, we discussed the role of Forkhead box (FOX) protein family in CDDP response. It has been reported that FOX proteins mainly promote CDDP resistance through the regulation of DNA repair, autophagy, epithelial-mesenchymal transition (EMT), and signaling pathways. Therefore, FOX proteins can be introduced as the prognostic markers to predict CDDP response in cancer patients. In addition, considering that oncogenic role of FOX proteins, the CDDP treatment along with FOX inhibition can be used as a therapeutic strategy in cancer patients.

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

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 Abstract.

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

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-ß. 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.

Role of forkhead box proteins in regulation of doxorubicin and paclitaxel responses in tumor cells: A comprehensive review.

Chemotherapy is one of the common first-line therapeutic methods in cancer patients. Despite the significant effects in improving the quality of life and survival of patients, chemo resistance is observed in a significant part of cancer patients, which leads to tumor recurrence and metastasis. Doxorubicin (DOX) and paclitaxel (PTX) are used as the first-line drugs in a wide range of tumors; however, DOX/PTX resistance limits their use in cancer patients. Considering the DOX/PTX side effects in normal tissues, identification of DOX/PTX resistant cancer patients is required to choose the most efficient therapeutic strategy for these patients. Investigating the molecular mechanisms involved in DOX/PTX response can help to improve the prognosis in cancer patients. Several cellular processes such as drug efflux, autophagy, and DNA repair are associated with chemo resistance that can be regulated by transcription factors as the main effectors in signaling pathways. Forkhead box (FOX) family of transcription factor has a key role in regulating cellular processes such as cell differentiation, migration, apoptosis, and proliferation. FOX deregulations have been associated with resistance to chemotherapy in different cancers. Therefore, we discussed the role of FOX protein family in DOX/PTX response. It has been reported that FOX proteins are mainly involved in DOX/PTX response by regulation of drug efflux, autophagy, structural proteins, and signaling pathways such as PI3K/AKT, NF-kb, and JNK. This review is an effective step in introducing the FOX protein family as the reliable prognostic markers and therapeutic targets in cancer patients.

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

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.

Molecular biology of microRNA-342 during tumor progression and invasion.

Cancer is considered as one of the main causes of human deaths and health challenges in the world. Various factors are involved in the high death rate of cancer patients, including late diagnosis and drug resistance that result in treatment failure and tumor recurrence. Invasive diagnostic methods are one of the main reasons of late tumor detection in cancer patients. Therefore, it is necessary to investigate the molecular tumor biology to introduce efficient non-invasive markers. MicroRNAs (miRNAs) are involved in regulation of the cellular mechanisms such as cell proliferation, apoptosis, and migration. MiRNAs deregulations have been also frequently shown in different tumor types. Here, we discussed the molecular mechanisms of miR-342 during tumor growth. MiR-342 mainly functions as a tumor suppressor by the regulation of transcription factors and signaling pathways such as WNT, PI3K/AKT, NF-kB, and MAPK. Therefore, miR-342 mimics can be used as a reliable therapeutic strategy to inhibit the tumor cells growth. The present review can also pave the way to introduce the miR-342 as a non-invasive diagnostic/prognostic marker in cancer patients.

Molecular mechanisms of microRNA-301a during tumor progression and metastasis.

Cancer is known as one of the leading causes of human deaths globally. Late diagnosis is considered as one of the main reasons for the high mortality rate among cancer patients. Therefore, the introduction of early diagnostic tumor markers can improve the efficiency of therapeutic modalities. MicroRNAs (miRNAs) have a key role in regulation of cell proliferation and apoptosis. MiRNAs deregulation has been frequently reported during tumor progressions. Since, miRNAs have a high stability in body fluids; they can be used as the reliable non-invasive tumor markers. Here, we discussed the role of miR-301a during tumor progressions. MiR-301a mainly functions as an oncogene via the modulation of transcription factors, autophagy, epithelial-mesenchymal transition (EMT), and signaling pathways. This review paves the way to suggest miR-301a as a non-invasive marker for the early tumor diagnosis. MiR-301a can also be suggested as an effective target in cancer therapy.

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

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.

Molecular mechanisms of microRNA-216a during tumor progression.

MicroRNAs (miRNAs) as the members of non-coding RNAs family are involved in post-transcriptional regulation by translational inhibiting or mRNA degradation. They have a critical role in regulation of cell proliferation and migration. MiRNAs aberrations have been reported in various cancers. Considering the importance of these factors in regulation of cellular processes and their high stability in body fluids, these factors can be suggested as suitable non-invasive markers for the cancer diagnosis. MiR-216a deregulation has been frequently reported in different cancers. Therefore, in the present review we discussed the molecular mechanisms of the miR-216a during tumor progression. It has been reported that miR-216a mainly functioned as a tumor suppressor through the regulation of signaling pathways and transcription factors. This review paves the way to suggest the miR-216a as a probable therapeutic and diagnostic target in cancer patients.

Prostate cancer, chronic myelogenous leukemia and multiple myeloma in a single patient: a case report and review of the literature.

BACKGROUND: Synchronous or metachronous multiple primary malignancies (MPMs) are a known phenomenon. These occurrences may be spontaneous or related to environmental risk factors or genetic predisposition. Chronic myelogenous leukemia (CML) and Multiple myeloma (MM) are two uncommon hematologic malignancies, arises from two different cell lineage. The coexistence of CML and MM that is a rare phenomenon, with only 29 cases reported in the literature. To the best of our, this combination of triple primary cancers has not been reported in a single patient. CASE PRESENTATION: Herein, we reported a case of an 85-year-old Iranian male with three confirmed primary malignant neoplasms. The patient presented with synchronous prostate cancer and CML, in august 2016. He received imatinib and nilotinib for CML and hormonal therapy for prostate cancer. He remained in good control at further follow-ups for about 5 years. In the follow-up period and after 61 months treatment with tyrosine kinase inhibitors (TKIs), CML was undetectable in molecular tests, but the presence of serum M-protein, abnormal plasma cells in the bone marrow, and CRAB criteria was compatible with MM. CONCLUSION: We must evaluate the possibility of multiple primary cancers during cancer treatment and follow-up and it may be worthwhile to monitor serum electrophoresis and protein levels in TKIs-treated patients.

MicroRNA-377: A therapeutic and diagnostic tumor marker.

Cancer is considered as one of the main causes of human deaths globally. Despite the recent progresses in therapeutic modalities, there is still a high rate of mortality among cancer patients. Late diagnosis in advanced tumor stages is one of the main reasons for treatment failure in cancer patients. Therefore, it is required to suggest the novel strategies for the early tumor detection. MicroRNAs (miRNAs) have critical roles in neoplastic transformation by regulation of cell proliferation, migration, and apoptosis. They are always considered as non-invasive markers due to their high stability in body fluids. Since, all of the miRNAs have tissue-specific functions in different tumors as tumor suppressor or oncogene; it is required to investigate the molecular mechanisms of every miRNA in different tumors to introduce that as a suitable non-invasive diagnostic marker in cancer patients. For the first time in the present review, we discussed the role of miR-377 during tumor progression. It has been reported that miR-377 mainly functions as a tumor suppressor through the regulation of signaling pathways and transcription factors. This review is an important step toward introducing the miR-377 as a novel diagnostic marker as well as a therapeutic target in cancer patients.