Review

Molecular themes in oncogenesis

Cancer has become a prominent cause of death, accounting for approximately 10 million deaths worldwide as per the World Health Organization report 2020. Epigenetics deal with the alterations of heritable phenotypes, except for DNA alterations. Currently, we are trying to comprehend the role of utmost significant epigenetic genes involved in the burgeoning of human cancer. A sundry of studies have reported the Enhancer of Zeste Homologue2 (EZH2) as a prime catalytic subunit of Polycomb Repressive Complex2, which is involved in several pivotal activities, including embryogenesis. In addition, EZH2 has detrimental effects leading to the onset and metastasis of several cancers. Jumonji AT Rich Interacting Domain2 (JARID2), an undebated crucial nuclear factor, has strong coordination with the PRC2 family. In this review, we discuss various epigenetic entities, primarily focusing on the possible role and mechanism of EZH2 and the significant contribution of JARID2 in human cancers.

The ability of viruses to evolve several orders of magnitude faster than their host cells has enabled them to exploit host cellular machinery by selectively recruiting multiprotein complexes (MPCs) for their catalyzed assembly and replication. This hijacking may depend on alternative, ‘moonlighting’ functions of host proteins that deviate from their canonical functions thereby inducing cellular pathology. Here, we posit that if virus-induced cellular pathology is similar to that of other, unknown (non-viral) causes, the identification and molecular characterization of the host proteins involved in virus-mediated cellular pathology can be leveraged to decipher the non-viral disease-relevant mechanisms. We focus on how virus-induced aberrant proteostasis and protein aggregation resemble the cellular pathology of sporadic neurodegenerative diseases (NDs) and how this can be exploited for drug discovery.

The Ski (Sloan-Kettering Institute) is an evolutionarily conserved protein that plays a dual role as an oncoprotein and tumor suppressor gene in the development of human cancer. The Ski oncogene was first identified as a transforming protein of the avian Sloan-Kettering retrovirus in 1986. Since its discovery, Ski has been identified as a carcinogenic regulator in a variety of malignant tumors. Later, it was reported that Ski regulates the occurrence and development of some cancers by acting as an oncogene. Ski mediates the proliferation, differentiation, metastasis, and invasion of numerous cancer cells through various mechanisms. Several studies have shown that Ski expression is correlated with the clinical characteristics of cancer patients and is a promising biomarker and therapeutic target for cancer. In this review, we summarize the mechanisms and potential clinical implications of Ski in dimorphism, cancer occurrence, and progression in various types of cancer.

Oil cakes, also known as defatted seeds used as by-product and has not studied against oral squamous cell carcinoma (OSCC). In present study, polyphenolic flavonoids of defatted seed extracts of Ocimum sanctum were investigated. Prepared extracts were analysed for thin layer chromatography & high pressure liquid chromatography to identify the polyphenolic flavonoid in extracts. In vitro antioxidant activity and in silico studies were observed by molecular docking with receptors of OSCC using Swiss docking and its pharmacokinetic screening. Present study revealed that quercetin, rutin and tannic acid were found in the defatted seed extracts. Antioxidant capacity was found to be high in ethanolic and aqueous extract of defatted seeds extract, whereas ethanolic extract has shown enzymatic activity and maximum level of non enzyme content in treated rat PC-12 cells that were exposed to neurotoxic shock. Molecular docking of quercetin, rutin and tannin acid has shown best binding energy results with epidermal growth factor receptor (EGFR), β2 adrenergic receptor (β2-AR) and keap1/nrf2 receptors of OSCC. Authors would to conclude that polyphenolic flavonoids has proven its antioxidant activity with rat PC-12 cells as well has revealed its binding efficacy against receptors that can be utilize against OSCC as herbal remedy.

Alternative polyadenylation (APA) is a novel mechanism in the expressional regulation of most human oncogenes. This process also is involved in cancer progression and prognosis. The potential of APA events as novel prognostic biomarkers has been suggested. CCND2 gene, which is overexpressed in various cancer tissues, tends to utilize the proximal APA site and produces a more prominent mRNA isoform with shorter 3’ untranslated region in the cancer cells. In this study, an ultrasensitive detection for CCND2 APA was successfully achieved using electrochemical biosensors constructed by gold nanoparticles-Fe₃O₄ nanocomposite and p-sulfonated calix[8]arene functionalized reduced graphene oxide as nanocarriers. The detection ranges of CCND2-S and CCND2-L by the constructed biosensors were 10⁻¹⁸–10⁻¹¹ and 10⁻¹⁷–10⁻¹¹ M, respectively. The limit of detection (LOD) of CCND2-S was 0.176 aM (the RNA concentration at the single-cell level). To the best of our knowledge, this value was the lowest LOD among the reported non-coding RNA detection. In real samples, the results of the electrochemical detection using the constructed biosensors showed that the lung cancer cell H292 expressed considerably higher CCND2-S than CCND2-L. This result was in agreement with those obtained by RT-qPCR method. The electrochemical method had showed simpler operation, accurate quantitation, faster detection, and cheaper supplies compared with traditional methods. Therefore, this technology not only provides an ultrasensitive and feasible method for APA detection, but can also be applied in the prognosis and diagnosis of cancer progression.