Majority of the human genome is transcribed to RNAs that do not encode proteins. These non-coding RNAs (ncRNAs) play crucial roles in regulating the initiation and progression of various cancers. Given the importance of the ncRNAs, the roles of ncRNAs in cancers have been reviewed elsewhere. Thus, in this review, we mainly focus on the recent studies of the function, regulatory mechanism and therapeutic potential of the ncRNAs including microRNA (miRNA), long ncRNA (lncRNA), circular RNA (circRNA) and PIWI interacting RNA (piRNA), in different type of cancers.

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Non-coding RNA in cancer.

Cervical cancer (CC) is one of the most common gynecological tumors that threatens women's health and lives. Aberrant expression of PIWI-interacting RNA (piRNA) is closely related with a range of cancers and can serve as a tumor promoter or suppressor in proliferation, migration and invasion. In this study, the aim was not only to discover differential expression of piRNA in CC tissue (CC cells) and normal cervical tissue (normal cervical epithelium cells), but also to investigate the biological function and action mechanism of piRNA in CC.The DESeq2 approach was used to estimate fold change in piRNA between CC tissue and normal cervical tissue. The relative expressions of piRNAs (piRNA-20657, piRNA-20497, piRNA-14633 and piRNA-13350) and RNA m6A methyltransferases/demethylases were detected using RT-qPCR. After intervention with piRNA-14633 and METTL14 expression, the viability of CaSki cells and SiHa cells was detected by CCK8. CC cell proliferation was detected by colony formation assay. Apoptosis rate and cell cycle were detected by flow cytometry. Transwell assay was performed to detect cell migration and invasion. EpiQuik m6A RNA Methylation Quantification Kit was used to evaluate m6A RNA methylation levels. Expression of methyltransferase-like protein 14 (METTL14), PIWIL-proteins and CYP1B1 were detected by RT-qPCR and western blot. The effect of piRNA-14633 on METTL14 was evaluated by a dual-luciferase reporter assay. The in vivo effects of piRNA-14633 on CC was assessed by nude mice experiments.piRNA-14633 showed high expression in CC tissues and cells, piRNA-14633 mimic (piRNA-14633 overexpression) promoted viability, proliferation, migration and invasion of CaSki cells and SiHa cells. Besides, piRNA-14633 mimic increased m6A RNA methylation levels and METTL14 mRNA stability. Results of dual luciferase reporter assays indicated that METTL14 was a directed target gene of piRNA-14633. Knockdown of METTL14 with siRNA attenuated proliferation, migration and invasion of CC cells. piRNA-14633 increased CYP1B1 expression, while silencing of METTL14 impaired its expression. The effect of piRNA overexpression on METTL14 expression has concentration-dependent characteristics. Results from in vivo experiment indicated that piRNA-14633 promoted cervical tumor growth.piRNA-14633 promotes proliferation, migration and invasion of CC cells by METTL14/CYP1B1 signaling axis, highlighting the important role of piRNA-14633 in CC. 

/pdf/pirna-14633-promotes-cervical-cancer-cell-malignancy-in-a-204kcihm.pdf

piRNA-14633 promotes cervical cancer cell malignancy in a METTL14-dependent m6A RNA methylation manner

/pdf/pirna-14633-promotes-cervical-cancer-cell-malignancy-in-a-162fjcmp.pdf

Whole transcriptome sequencing analysis revealed key RNA profiles and toxicity in mice after chronic exposure to microplastics.

PIWI-interacting RNAs and PIWI proteins in diabetes and cardiovascular disease: Molecular pathogenesis and role as biomarkers.

PIWI-interacting RNAs (piRNAs) are a kind of non-coding small RNAs, which play a biological role by specifically binding to PIWI proteins. Studies have demonstrated that piRNAs play a significant role in germline cell growth by repressing transposable elements, especially in the regulation of DNA methylation. Recently increasing evidence revealed that piRNAs involved in the regulation of cell proliferation, apoptosis, and cycle; however, the mechanism of piRNAs is unclear. This review summarizes the research progress regarding the roles of piRNAs in the cell proliferation, apoptosis, and cycle.

https://iubmb.onlinelibrary.wiley.com/doi/pdf/10.1002/iub.2332

Role of PIWI-interacting RNAs on cell survival: Proliferation, apoptosis, and cycle

CircRNAs in diabetic cardiomyopathy.

MicroRNA-223-3p promotes pyroptosis of cardiomyocyte and release of inflammasome factors via downregulating the expression level of SPI1 (PU.1).

Farnesoid X receptors (FXR) are bile acid receptors that play roles in lipid, glucose, and energy homeostasis. Synthetic FXR-specific agonists have been developed for treating nonalcoholic fatty liver disease (NAFLD) patients. However, the detailed mechanism remains unclear. To investigate the effects of FXR on NAFLD and the possible mechanism, FXR-null mice were fed either a normal or a high-fat diet. The FXR-null mice developed hepatomegaly, steatosis, accumulation of lipid droplets in liver cells, glucose metabolism disorder, and elevated serum lipid levels. Transcriptomic results showed increased expression of key lipid synthesis and glucose metabolism-related proteins. We focused on pyruvate dehydrogenase kinase 4 (PDK4), a key enzyme involved in the regulation of glucose and fatty acid (FA) metabolism and homeostasis. Subsequently, we confirmed an increase in PDK4 expression in FXR knockout cells. Moreover, inhibition of PDK4 expression alleviated lipid accumulation in hepatocytes caused by FXR deficiency in vivo and in vitro. Our results identify FXR as a nuclear transcription factor that regulates glucose and lipid metabolism balance through PDK4, providing further insights into the mechanism of FXR agonists in the treatment of metabolic diseases.

/pdf/farnesoid-x-receptor-deficiency-induces-hepatic-lipid-and-1h7yicwg.pdf

Hengquan Wan

Papers

Role of PIWI-interacting RNAs on cell survival: Proliferation, apoptosis, and cycle

PIWI-interacting RNAs and PIWI proteins in diabetes and cardiovascular disease: Molecular pathogenesis and role as biomarkers.

CircRNAs in diabetic cardiomyopathy.

MicroRNA-223-3p promotes pyroptosis of cardiomyocyte and release of inflammasome factors via downregulating the expression level of SPI1 (PU.1).

Farnesoid X Receptor Deficiency Induces Hepatic Lipid and Glucose Metabolism Disorder via Regulation of Pyruvate Dehydrogenase Kinase 4