MicroRNAs (miRNAs) are endogenous ∼23 nt RNAs that play important gene-regulatory roles in animals and plants by pairing to the mRNAs of protein-coding genes to direct their posttranscriptional repression. This review outlines the current understanding of miRNA target recognition in animals and discusses the widespread impact of miRNAs on both the expression and evolution of protein-coding genes.

MicroRNAs: Target Recognition and Regulatory Functions

Fungi are known to produce a wide range of secondary metabolites such as pigments, antibiotics, vitamins, amino acids, and organic compounds that have several useful biological activities such as antifungal, antiinflammatory, antioxidant, antimicrobial, and anticancer and also have wide range of biotechnological applications in food, pharmaceutical, and cosmetic industries as well as in agriculture. Antibiotics such as β-lactam, cholesterol-lowering drug, lovastatin, and penicillin are some of the important fungal metabolites that have diverse biotechnological applications in pharmaceutical industries and in the field of medicine. On the other hand, several of these fungal secondary metabolites also have potentially harmful biological activities such as mycotoxins and phytotoxins. There are various biosynthetic pathways followed by the fungi to produce secondary metabolites such as β-lactam, cyclic peptide, diterpenes, diketopiperazines, polyketides, sesquiterpenes, and a combination of these pathways. There are wide ranges of fungal communities producing potentially important secondary metabolites including Penicillium notatum, Cephalosporium acremonium, Penicillium griseofulvum, Streptomyces griseus, Monascus purpureus, Micromonospora purpurea, Tolypocladium inflatum, Aspergillus niger, Aspergillus parasiticus, and Beauveria bassiana. The potential biological applications of secondary metabolites of fungi will be useful for sustainable development.

Fungal secondary metabolites and their biotechnological applications for human health

Cancer is one of the most important healthcare matters, with the worst prognosis but the best possibilities for scientific development. It is likely to increase in the future and cause global havoc designating it as an epidemic. Cancer development requires urgent intervention. Past few decades have witnessed extensive research to challenge carcinogenesis. Treatment involving synthetic discipline is often associated with severe adverse effects, or even worsened prognosis. Accordingly, newer economic and patient friendly molecules are warranted. Many natural substances have proved their potential so far. Cucurbitacin B against cancer and other diseases has achieved towering popularity among the researchers around the world, as detailed in the below sections with summarized tables. In line with the fascinating role of cucurbitacin B against various types of cancers, through various molecular signaling pathways, it is justifiable to propose cucurbitacin B as a mainline chemotherapy before the onset and after the diagnosis of cancer.

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Cucurbitacin B and cancer intervention: Chemistry, biology and mechanisms (Review).

Chlorogenic acid complex (CGA7), standardized extract from green coffee beans exerts anticancer effects against cultured human colon cancer HCT-116 cells

Cellular senescence is a state of permanent cell-cycle arrest triggered by different internal and external stimuli. This phenomenon is considered to be both beneficial and detrimental depending on the cell types and biological contexts. During normal embryonic development and after tissue injury, cellular senescence is critical for tissue remodeling. In addition, this process is useful for arresting growth of tumor cells, particularly during early onset of tumorigenesis. However, accumulation of senescent cells decreases tissue regenerative capabilities and induces inflammation, which is responsible for cancer and organismal aging. Therefore cellular senescence has to be tightly regulated, and dysregulation might lead to the aging and human diseases. Among many regulators of cellular senescence, in this review, I will focus on microRNAs, small non-coding RNAs playing critical roles in diverse biological events including cellular senescence. [BMB Reports 2018; 51(10): 494-500].

MicroRNA controls of cellular senescence.

Helicteres angustifolia L. is a shrub that forms a common ingredient of several cancer treatment recipes in traditional medicine system both in China and Laos. In order to investigate molecular mechanisms of its anticancer activity, we prepared aqueous extract of Helicteres angustifolia L. Roots (AQHAR) and performed several in vitro assays using human normal fibroblasts (TIG-3) and osteosarcoma (U2OS). We found that AQHAR caused growth arrest/apoptosis of U2OS cells in a dose-dependent manner. It showed no cytotoxicity to TIG-3 cells at doses up to 50 μg/ml. Biochemical, imaging and cell cycle analyses revealed that it induces ROS signaling and DNA damage response selectively in cancer cells. The latter showed upregulation of p53, p21 and downregulation of Cyclin B1 and phospho-Rb. Furthermore, AQHAR-induced apoptosis was mediated by increase in pro-apoptotic proteins including cleaved PARP, caspases and Bax. Anti-apoptotic protein Bcl-2 showed decrease in AQHAR-treated U2OS cells. In vivo xenograft tumor assays in nude mice revealed dose-dependent suppression of tumor growth and lung metastasis with no toxicity to the animals suggesting that AQHAR could be a potent and safe natural drug for cancer treatment.

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Functional Characterisation of Anticancer Activity in the Aqueous Extract of Helicteres angustifolia L. Roots

microRNAs (miRs) have recently emerged as small non-coding regulators of gene expression. We performed a loss-of-function screening by recruiting retrovirus mediated arbitrary manipulation of genome coupled with escape of cells from 5-Aza-2′-deoxycytidine (5-Aza-dC)-induced senescence. miRNA pool from cells that emerged from 5-Aza-dC-induced senescence was subjected to miR-microarray analysis with respect to the untreated control. We identified miR-451 as one of the upregulated miRs and characterized its functional relevance to drug resistance, cell growth, tumor suppressor proteins p53 and pRb, and stress response. We report that miR-451 caused growth arrest in cells leading to their resistance to 5-Aza-dC-induced senescence. Decrease in cyclin D1, CDK4 and phosphorylated pRB supported the growth arrest in miR-451 transfected cells. We demonstrate that Collaborator of ARF (CARF) protein is a new target of miR-451 that intermediates its function in tumor suppressor and stress signaling.

/pdf/tumor-suppressor-activity-of-mir-451-identification-of-carf-2gm93hyode.pdf

Tumor suppressor activity of miR-451: Identification of CARF as a new target.

Significance of microRNAs (miRs), small non-coding molecules, has been implicated in a variety of biological processes. Here, we recruited retroviral insertional mutagenesis to obtain induction of an arbitrary noncoding RNAs, and coupled it with a cell based loss-of-function (5-Aza-2'-deoxycytidine (5Aza-dC)-induced senescence bypass) screening system. Cells that escaped 5-Aza-dC-induced senescence were subjected to miR-microarray analysis with respect to the untreated control. We identified miR-335 as one of the upregulated miRs. In order to characterize the functional significance, we overexpressed miR-335 in human cancer cells and found that it caused growth suppression. We demonstrate that the latter accounted for inhibition of 5-Aza-dC incorporation into the cell genome, enabling them to escape from induction of senescence. We also report that CARF (Collaborator of ARF) is a new target of miR-335 that regulates its growth suppressor function by complex crosstalk with other proteins including p16(INK4A), pRB, HDM2 and p21(WAF1).

/pdf/loss-of-function-screening-to-identify-mirnas-involved-in-4odo6h9cl1.pdf

Yue Yu

Papers

Functional Characterisation of Anticancer Activity in the Aqueous Extract of Helicteres angustifolia L. Roots

Tumor suppressor activity of miR-451: Identification of CARF as a new target.

Loss-of-function screening to identify miRNAs involved in senescence: tumor suppressor activity of miRNA-335 and its new target CARF

by Induction of Genes Involved in K (hnRNP-K) Promotes Tumor Metastasis Heterogeneous Nuclear Ribonucleoprotein