Pre-clinical and clinical importance of miR-21 in human cancers: Tumorigenesis, therapy response, delivery approaches and targeting agents.

The field of non-coding RNA (ncRNA) has made significant progress in understanding the pathogenesis of diseases and has broadened our knowledge towards their targeting, especially in cancer therapy. ncRNAs are a large family of RNAs with microRNAs (miRNAs) being one kind of endogenous RNA which lack encoded proteins. By now, miRNAs have been well-coined in pathogenesis and development of cancer. The current review focuses on the role of miR-21 in cancers and its association with tumor progression. miR-21 has both oncogenic and onco-suppressor functions and most of the experiments are in agreement with the tumor-promoting function of this miRNA. miR-21 primarily decreases PTEN expression to induce PI3K/Akt signaling in cancer progression. Overexpression of miR-21 inhibits apoptosis and is vital for inducing pro-survival autophagy. miR-21 is vital for metabolic reprogramming and can induce glycolysis to enhance tumor progression. miR-21 stimulates EMT mechanisms and increases expression of MMP-2 and MMP-9 thereby elevating tumor metastasis. miR-21 is a target of anti-cancer agents such as curcumin and curcumol and its down-regulation impairs tumor progression. Upregulation of miR-21 results in cancer resistance to chemotherapy and radiotherapy. Increasing evidence has revealed the role of miR-21 as a biomarker as it is present in both the serum and exosomes making them beneficial biomarkers for non-invasive diagnosis of cancer.

Crosstalk of miRNAs with signaling networks in bladder cancer progression: Therapeutic, diagnostic and prognostic functions.

Urological cancers are considered as life-threatening diseases around the world. Bladder cancer is one of the most malignant urological tumors with high mortality and morbidity. Bladder cancer is a heterogenous disease and genetic alterations have shown to be key players in regulating its progression. Although conventional therapies are somewhat beneficial in improving prognosis and survival, bladder cancer patients suffer from recurrence. MicroRNAs (miRNAs) are endogenous short RNA molecules that do not encode proteins and show dysregulated expression in human cancers. miRNAs are regulators of vital biological processes in cells such as proliferation, migration, differentiation and apoptosis. Dysregulation of miRNAs is observed in bladder cancer and they are used as biomarkers for diagnosis and prognosis of patients. LncRNAs and circRNAs are modulators of bladder cancer progression via miRNA expression regulation. Overexpression of onco-suppressor miRNAs impairs bladder cancer progression, while oncogenic miRNAs drive tumor progression. Glycolysis and EMT mechanisms are two important factors for proliferation and migration of bladder cancer that are modulated by miRNAs. Furthermore, miRNAs can affect STAT3 and Wnt/ß-catenin as instances of molecular factors in regulating bladder tumor progression. Bladder tumor response to drug therapy and radiotherapy is regulated by miRNAs. Hence, aim of current review is to provide function of miRNAs in bladder cancer based on their crosstalk with other molecular pathways and interaction with biological processes.

Long non-coding RNA/epithelial-mesenchymal transition axis in human cancers: Tumorigenesis, chemoresistance, and radioresistance.

Epithelial-to-mesenchymal transition (EMT) is a process that involves the transformation of polarized epithelial cells to attain a mesenchymal phenotype that presents an elevated migratory potential, invasiveness, and antiapoptotic properties. Many studies have demonstrated that EMT is a prominent event that is associated with embryogenesis, tumor progression, metastasis, and therapeutic resistance. The EMT process is driven by key transcription factors (such as Snail, Twist, ZEB, and TGF-ß) and several long non-coding RNAs (lncRNAs) in many non-pathological as well as pathological conditions. In the present report, we have comprehensively discussed the oncogenic and tumor suppressor role of lncRNAs and their mechanism of action in the regulation of the EMT process in various cancers such as brain tumors, gastrointestinal tumors, and gynecological and urological tumors. We have also elaborated on the role of lncRNAs in the regulation of EMT-related transcription factors (such as Snail, Twist, ZEB, and TGF-ß) and therapeutic response (chemoresistance and radioresistance). Lastly, we have emphasized the role of exosomal lncRNAs in the regulation of EMT, metastasis, and therapeutic response in the aforementioned cancers. Taken together, this review provides a detailed insight into the understanding of role of lncRNAs/exosomal lncRNAs in EMT, metastasis, and therapeutic response in human cancers.

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.

Expression of Treg-associated lncRNAs in breast cancer.

Regulatory T cells (Tregs) have important functions in tumor microenvironment, particularly for induction of immune evasion. In order to find the underlying mechanism of dysregulation of Tregs in breast cancer tissues, we designed the current study to appraise expression of five Treg-related long non-coding RNAs (lncRNAs), namely FLICR (FOXP3 Regulating Long Intergenic Non-Coding RNA), NEST (IFNG-AS1), RMRP (RNA Component of Mitochondrial RNA Processing Endoribonuclease), MAFTRR (MAF Transcriptional Regulator RNA) and TH2-LCR (Th2 Cytokine Locus Control Region) in paired breast cancer and nearby noncancerous tissues. Expression levels of RMRP, TH2-LCR, MAFTRR and GATA3-AS1 were significantly higher in breast cancer samples compared with non-tumoral tissues. The calculated AUC values for GATA3-AS1, TH2-LCR, RMRP and MAFTRR were 0.66, 0.63, 0.63 and 0.60, respectively. There were significant positive associations between expression level of RMRP gene in tumor tissues and nuclear grade, tubule formation and tumor sizes. In addition, there was a significant positive association between expression levels of MAFTRR genes in tumor tissues and nuclear grade. Besides, expression levels of FLICR were different among tumors with different levels of HER2/neu receptor. Taken together, Treg-associated lncRNAs might contribute to the pathogenesis of breast cancer.

EMT mechanism in breast cancer metastasis and drug resistance: Revisiting molecular interactions and biological functions.

One of the malignant tumors in women that has involved both developed and developing countries is breast cancer. Similar to other types of tumors, breast cancer cells demonstrate high metastatic nature. Besides, breast tumor cells have ability of developing drug resistance. EMT is the related mechanism to cancer metastasis and focus of current manuscript is highlighting function of EMT in breast tumor malignancy and drug resistance. Breast tumor cells increase their migration by EMT induction During EMT, N-cadherin and vimentin levels increase, and E-cadherin levels decrease to mediate EMT-induced breast tumor invasion. Different kinds of anti-cancer agents such as tamoxifen, cisplatin and paclitaxel that EMT induction mediates chemoresistance feature of breast tumor cells. Furthermore, EMT induction correlates with radio-resistance in breast tumor. Clinical aspect is reversing EMT in preventing chemotherapy or radiotherapy failure in breast cancer patients and improving their survival time. The anti-tumor agents that suppress EMT can be used for decreasing breast cancer invasion and increasing chemosensitivity of tumor cells. Furthermore, lncRNAs, miRNAs and other factors can modulate EMT in breast tumor progression that are discussed here.