The interplay of Klotho with signaling pathway and microRNAs in cancers

Abstract

Klotho (KL) gene has been accepted as an "aging suppressor" gene that encodes a single transmembrane protein in human known as Klotho which is commonly expressed in renal tubes. The interruption in the secretion of Klotho protein expedites aging whereas its high expression extends lifespan. The family of Klotho proteins has been reported to act as distinct receptors for endocrine fibroblast growth factors (FGFs), which manage multifarious metabolic processes. Further, the secreted Klotho is a hormonal factor that takes part in the ion channel organization. Numerous studies determined that this protein affects the function of a number of important signaling pathways, which may present an impact in tumorigenesis via the coordination of receptors located on them. This review article focuses on the effects of microRNAs on the performance of Klotho and how the interplay between Klotho and certain pathways like insulin‐like growth factor, FGF, Wnt, and transforming growth factor β contribute to the biogenesis of cancer. The present study is also pointed at defining the molecular mechanisms of these interactions.

Signaling, metabolism, and cancer: An important relationship for therapeutic intervention

“…To facilitate the Wnt signaling, co receptors such as LRP‐5/6 are required (MacDonald et al, 2009; Pedone & Marucci, 2019). B‐catenin can stimulate the expression of proto‐oncogenes such as c‐myc (Abolghasemi et al, 2019). B‐catenin also plays a key role in the aggression and metastasis (Jang et al, 2015; Yang et al, 2017).…”

Evaluation of L-fucose and Sialic Acid Levels in Patients With Colorectal Cancer and Control Subject

“…In this regard, it can be noted that in recent years, researchers have concentrated on the DNA damage response in cancer and some of the effective factors in the pathogenesis of the human disease [19,20]. There is increasing evidence to support the measurement of specific biomarkers in biological samples of patients with cancer [21,22]. Furthermore, researchers suggest that the regulatory functions of circular RNAs and targeting the mammalian target of rapamycin signaling are effective in cancer therapy [23,24].…”

Klotho Pathways, Myelination Disorders, Neurodegenerative Diseases, and Epigenetic Drugs

“…5,6,23,102,[139][140][141][142][143][144][145][146] FGFs are exemplary pleiotropic hormones that play numerous roles in cellular and metabolic homeostasis. 5,6,137,141,[144][145][146][147][148] In particular, FGF23 is a bone-derived hormone that in conjunction with Klotho acts on the kidney to increase phosphate excretion and suppress biosynthesis of vitamin D. 5,6,14,23,102,136,138,145,148,149 Vitamin D regulates epigenetic mechanisms that maintain the transcription of its target genes in regulatory networks, including the expression of Klotho and nuclear factor-erythroid-2related factor 2 (Nrf2) to carry out many of its homoeostatic functions. 17,97,[150][151][152][153] Vitamin D is a modulator of the immune system, 154,155 hence its mention here, and accumulating evidence suggests vitamin D deficiency is a risk factor for dysregulated Klotho-associated neurodegenerative diseases, the most noteworthy being MS. 9,27,52,97,…”