ABSTRACT
SOX transcription factors are critical regulators of development, homeostasis and disease progression and their dysregulation is a common finding in various cancers. SOX9 belongs to SOXE family located on chromosome 17. MicroRNAs (miRNAs) possess the capacity of regulating different transcription factors in cancer cells by binding to 3'-UTR. Since miRNAs can affect differentiation, migration, proliferation and other physiological mechanisms, disturbances in their expression have been associated with cancer development. In this review, we evaluate the relationship between miRNAs and SOX9 in different cancers to reveal how this interaction can affect proliferation, metastasis and therapy response of cancer cells. The tumor-suppressor miRNAs can decrease the expression of SOX9 by binding to the 3'-UTR of mRNAs. Furthermore, the expression of downstream targets of SOX9, such as c-Myc, Wnt, PI3K/Akt can be affected by miRNAs. It is noteworthy that other non-coding RNAs including lncRNAs and circRNAs regulate miRNA/SOX9 expression to promote/inhibit cancer progression and malignancy. The pre-clinical findings can be applied as biomarkers for diagnosis and prognosis of cancer patients.
Subject(s)
MicroRNAs/metabolism , Neoplasms/metabolism , SOX9 Transcription Factor/metabolism , Animals , Gene Expression Regulation, Neoplastic , Humans , MicroRNAs/genetics , Neoplasms/genetics , Neoplasms/pathology , RNA, Circular/genetics , RNA, Circular/metabolism , RNA, Long Noncoding/genetics , RNA, Long Noncoding/metabolism , SOX9 Transcription Factor/genetics , Signal TransductionABSTRACT
Doxorubicin (DOX) is a well-known chemotherapeutic agent extensively applied in the field of cancer therapy. However, similar to other chemotherapeutic agents such as cisplatin, paclitaxel, docetaxel, etoposide and oxaliplatin, cancer cells are able to obtain chemoresistance that limits DOX efficacy. In respect to dose-dependent side effect of DOX, enhancing its dosage is not recommended for effective cancer chemotherapy. Therefore, different strategies have been considered for reversing DOX resistance and diminishing its side effects. Phytochemical are potential candidates in this case due to their great pharmacological activities. Curcumin is a potential antitumor phytochemical isolated from Curcuma longa with capacity of suppressing cancer metastasis and proliferation and affecting molecular pathways. Experiments have demonstrated the potential of curcumin for inhibiting chemoresistance by downregulating oncogene pathways such as MMP-2, TGF-ß, EMT, PI3K/Akt, NF-κB and AP-1. Furthermore, coadministration of curcumin and DOX potentiates apoptosis induction in cancer cells. In light of this, nanoplatforms have been employed for codelivery of curcumin and DOX. This results in promoting the bioavailability and internalization of the aforementioned active compounds in cancer cells and, consequently, enhancing their antitumor activity. Noteworthy, curcumin has been applied for reducing adverse effects of DOX on normal cells and tissues via reducing inflammation, oxidative stress and apoptosis. The current review highlights the anticancer mechanism, side effects and codelivery of curcumin and DOX via nanovehicles.
ABSTRACT
Cancer is one of the life-threatening disorders that, in spite of excellent advances in medicine and technology, there is no effective cure for. Surgery, chemotherapy, and radiotherapy are extensively applied in cancer therapy, but their efficacy in eradication of cancer cells, suppressing metastasis, and improving overall survival of patients is low. This is due to uncontrolled proliferation of cancer cells and their high migratory ability. Finding molecular pathways involved in malignant behavior of cancer cells can pave the road to effective cancer therapy. In the present review, we focus on phosphatase and tensin homolog (PTEN) signaling as a tumor-suppressor molecular pathway in gastric cancer (GC). PTEN inhibits the PI3K/Akt pathway from interfering with the migration and growth of GC cells. Its activation leads to better survival of patients with GC. Different upstream mediators of PTEN in GC have been identified that can regulate PTEN in suppressing growth and invasion of GC cells, such as microRNAs, long non-coding RNAs, and circular RNAs. It seems that antitumor agents enhance the expression of PTEN in overcoming GC. This review focuses on aforementioned topics to provide a new insight into involvement of PTEN and its downstream and upstream mediators in GC. This will direct further studies for evaluation of novel signaling networks and their targeting for suppressing GC progression.
