Regulation of Kisspeptin mediated signaling by non-coding RNAs in different cancers: the beginning of a new era.

Kisspeptin-driven intracellular signaling has captured enormous attention because of its central role in cancer onset and progression. Wealth of information has helped us to develop a better understanding of the critical roles of Kisspeptin-mediated signaling in different cancers. However, astonishingly, we have not yet drilled down deep into the mysterious aspects associated with non-coding RNA mediated regulation of Kisspeptin-driven signaling. Therefore, in this mini-review, we will comprehensively analyze available evidence related to miRNAs and long non-coding RNAs (LncRNAs) and their ability to modulate Kisspeptin-mediated signaling. There are visible knowledge gaps about interplay between non-coding RNAs and Kisspeptin-mediated signaling. It will be appropriate to say that we have just started to scratch the surface of an entirely new regulatory layer of Kisspeptin-mediated transduction cascade. Mechanistically, it has been revealed that inhibition of Kisspeptin mediated signaling activated and stimulated the entry of NFκB into the nucleus to stimulate expression of proteins which can sequentially inactivate tumor suppressor miRNAs. miRNAs have also an instrumental role in regulation of proteins which post-translationally modify and inhibit KISS1 expression. It is becoming progressively more understandable that LncRNAs act as miRNA sponges and protect oncogenic mRNAs. However, these facets are also incompletely investigated. Identification of LncRNAs which interfere with Kisspeptin-mediated pathway either through acting as miRNA sponges or working with methylation-associated machinery will be helpful in sharpening the resolution of the pixels of the regulatory network which shapes Kisspeptin-mediated signaling.

Regulation of Cell Signaling Pathways by Berberine in Different Cancers: Searching for Missing Pieces of an Incomplete Jig-Saw Puzzle for an Effective Cancer Therapy.

There has been a renewed interest in the identification of natural products having premium pharmacological properties and minimum off-target effects. In accordance with this approach, natural product research has experienced an exponential growth in the past two decades and has yielded a stream of preclinical and clinical insights which have deeply improved our knowledge related to the multifaceted nature of cancer and strategies to therapeutically target deregulated signaling pathways in different cancers. In this review, we have set the spotlight on the scientifically proven ability of berberine to effectively target a myriad of deregulated pathways.

Bioactivity evaluation and HPLC UV-VIS based quantification of antioxidant secondary metabolites from extract and fractions of Bistorta amplexicaulis rhizome.

Bistorta amplexicaulis is a popular medicinal plant and reported as rich source of antioxidant compounds. The present study was designed for antioxidant and anticancer potential of polarity based fractions of B. amplexicaulis and its correlation to the secondary metabolites quantified by HPLC-UV/VIS.Crude extract was prepared by maceration method and polarity based fractions were prepared by solvent-solvent extraction. Antioxidant and anticancer potential was investigated by using various physiological and non-physiological assays while secondary metabolites rutin, naringin and quercetin present in extract and fractions were quantified by using HPLC- UV/VIS. All extracts showed Antioxidant potential but highest activity was obtained with ethyl acetate fraction (DPPH IC50 5.76±0.03 µg/ml, ABTS IC50 0.74±0.1 µg/ml, Total Antioxidant Assay 72.55±0.098 Ascorbic acid equivalents, Super oxide radical scavenging assay IC506.86±0.1909 µg/ml, Hydroxyl radical scavenging assay IC50 0.96±0.1690 µg/ml). The cytotoxicity of fractions against HepG2 cell lines showed lowest ell viability in n-hexane fraction (11%). The results revealed that ethyl acetate fraction of B. amplexicaulis can be a potential source of novel antioxidant compounds while n hexane fraction could provide anticancer compounds. A new method of simultaneous quantification of three flavonoids by using UV/VIS detector is reported in this study.

Interplay of long non-coding RNAs and TGF/SMAD signaling in different cancers.

Based on the exciting insights gleaned from decades of ground-breaking research, it has become evident that deregulated signaling pathways play instrumental role in cancer development and progression. Interestingly discovery of non-coding RNAs has revolutionized our understanding related to transcription, post-transcription and translation. Modern era has witnessed landmark discoveries in the field of molecular cancer and non-coding RNA biology has undergone tremendous broadening. There has been an exponential growth in the list of publications related to non-coding RNAs and overwhelmingly increasing classes of non-coding RNAs are adding new layers of complexity to already complicated nature of cancer. Regulation of TGF/SMAD signaling by miRNAs and LncRNAs has opened new horizons for therapeutic targeting of TGF/SMAD pathway. In this review we have set spotlight on central role of LncRNAs in modulation of TGF/SMAD pathway. Major proportion of the available evidence is underlining positive role of LncRNAs in contextual regulation of TGF/SMAD pathway. LncRNAs are vital to these regulatory networks because they provide a background support to make the TGF/SMAD mediated intracellular signaling more smooth or make transduction cascade more flexible in response to cues from extracellular environment. Therefore, in accordance with this notion, MALAT1, OIP5-AS1, MIR100HG, HOTAIR, ANRIL, PVT1, AFAP1-AS1, SPRY4-IT, ZEB2NAT, TUG1 and Lnc-SNHG1 have been reported to positively regulate TGF/SMAD signaling. In this review, we have focused on the regulation of TGF/SMAD signaling by LncRNAs and how these non-coding RNAs can be therapeutically exploited. Short-interfering RNA (siRNA) and natural products are currently being tested for efficacy against different LncRNAs. Nanotechnological strategies to efficiently deliver LncRNA-targeting siRNAs are also currently being investigated in different cancers.