Crosstalk between long noncoding RNA and microRNA in Cancer.

miRNAs and lncRNAs play a central role in cancer-associated gene regulations. The dysregulated expression of lncRNAs has been reported as a hallmark of cancer progression, acting as an independent prediction marker for an individual cancer patient. The interplay of miRNA and lncRNA decides the variation of tumorigenesis that could be mediated by acting as sponges for endogenous RNAs, regulating miRNA decay, mediating intra-chromosomal interactions, and modulating epigenetic components. This paper focuses on the influence of crosstalk between lncRNA and miRNA on cancer hallmarks such as epithelial-mesenchymal transition, hijacking cell death, metastasis, and invasion. Other cellular roles of crosstalks, such as neovascularization, vascular mimicry, and angiogenesis were also discussed. Additionally, we reviewed crosstalk mechanism with specific host immune responses and targeting interplay (between lncRNA and miRNA) in cancer diagnosis and management.

Cellular landscaping of cisplatin resistance in cervical cancer.

Cervical cancer (CC) caused by human papillomavirus (HPV) is one of the largest causes of malignancies in women worldwide. Cisplatin is one of the widely used drugs for the treatment of CC is rendered ineffective owing to drug resistance. This review highlights the cause of resistance and the mechanism of cisplatin resistance cells in CC to develop therapeutic ventures and strategies that could be utilized to overcome the aforementioned issue. These strategies would include the application of nanocarries, miRNA, CRIPSR/Cas system, and chemotherapeutics in synergy with cisplatin to not only overcome the issues of drug resistance but also enhance its anti-cancer efficiency. Moreover, we have also discussed the signaling network of cisplatin resistance cells in CC that would provide insights to develop therapeutic target sites and inhibitors. Furthermore, we have discussed the role of CC metabolism on cisplatin resistance cells and the physical and biological factors affecting the tumor microenvironments.

Phage delivered CRISPR-Cas system to combat multidrug-resistant pathogens in gut microbiome.

The Host-microbiome interactions that exist inside the gut microbiota operate in a synergistic and abnormal manner. Additionally, the normal homeostasis and functioning of gut microbiota are frequently disrupted by the intervention of Multi-Drug Resistant (MDR) pathogens. CRISPR-Cas (CRISPR-associated protein with clustered regularly interspersed short palindromic repeats) recognized as a prokaryotic immune system has emerged as an effective genome-editing tool to edit and delete specific microbial genes for the expulsion of bacteria through bactericidal action. In this review, we demonstrate many functioning CRISPR-Cas systems against the anti-microbial resistance of multiple pathogens, which infiltrate the gastrointestinal tract. Moreover, we discuss the advancement in the development of a phage-delivered CRISPR-Cas system for killing a gut MDR pathogen. We also discuss a combinatorial approach to use bacteriophage as a delivery system for the CRISPR-Cas gene for targeting a pathogenic community in the gut microbiome to resensitize the drug sensitivity. Finally, we discuss engineered phage as a plausible potential option for the CRISPR-Cas system for pathogenic killing and improvement of the efficacy of the system.

Mechanistic role of HPV-associated early proteins in cervical cancer: Molecular pathways and targeted therapeutic strategies.

PURPOSE: Cervical cancer (CC), one of the major causes of death of women throughout the world is primarily caused due to Human Papilloma Virus (HPV) 16 and 18. The early region (E) oncoproteins of HPV are associated with the etiopathogenesis and contribute to the progression of cancer. The present article comprehensively discussed the structural organization and biological functions of all E proteins of HPV and their contribution to progression of CC with an intent to decipher the pathological hallmarks and their relationship. Additionally, the role of E proteins in reference to therapeutics will also be presented. METHODS: A systematic search has been carried out for articles published in PubMed database by using combinations of different keywords with Boolean operators (AND, OR, NOT) including cervical cancer, HPV, E proteins, and signaling. RESULTS: From the analysis of literature review, its apparent that E proteins are the major contributor to disease progression. E1, E2, and E4 forms are mainly associated with viral integration, replication, and transcription whereas E6 and E7 act as an oncoprotein and are associated with the progression of cancer. E5 regulates cell proliferation, apoptosis, and facilitates the activity of E6 and E7. Additionally, E proteins were observed associated with numerous cell signaling pathways including PI3K/AKT, Wnt, Notch and reasonably contribute to the initiation of malignancy, cell proliferation, metastasis, and drug resistance. Knowing the role and interplay of each protein in initiation to progression of CC, their therapeutic significance has been elucidated. The present study observations demonstrate that E6 and E7 are the major cause of HPV-mediated CC progression. E1, E2, and E5 also act as a backbone for E6 and E7 and most of the current approaches have targeted E6 and E7 mediated action only. CONCLUSION: The present review illustrates the structural organization as well as function and regulation of all early proteins of HPV and their association with several cellular signaling pathways. The observations provide clue on the regulatory aspect of these proteins in initiation to progression and reasonably represent that targeting these proteins could be a novel therapeutic strategy for CC. In particular, its seemingly appears that inhibition of the activity of E6 and E7 oncoproteins may be a better selective target to delay the progression of CC. The review reaffirms the role of E proteins and encourages future studies on developing diagnostics, and most importantly therapeutics strategies targeting E6 and E7 oncoproteins to tackle CC related morbidity and mortality.