Nuclear paraspeckle assembly transcript 1 (NEAT1), a long non-coding RNA (lncRNA), is a core structural component of paraspeckles and is essential for paraspeckle formation. NEAT1 comprises two different isoforms: NEAT1_1 (3.7 kb) and NEAT1_2 (23 kb). Recently, NEAT1 has been shown to have oncogenic roles and to facilitate tumorigenesis in various human cancers. However, the function of NEAT1 in papillary thyroid cancer (PTC) is not well understood. The relative expression levels of NEAT1_2, ATPase family AAA domain-containing protein 2 (ATAD2), and microRNA-106b-5p (miR-106b-5p) were assessed via quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR). Four PTC cell lines were used to detect the relative expression of NEAT1_2. The effects of NEAT1_2 on PTC cells were studied by RNA interference approaches in vitro. The effects of NEAT1_2 on downstream proteins were detected by western blotting. The underlying mechanism was clarified by a rescue experiment, and three dual-luciferase reporter assays. NEAT1_2 expression was markedly increased in PTC tissues and the PTC cell lines (K1 and TPC1). The relative expression level of NEAT1_2 was positively associated with TNM stage and tumor size. NEAT1_2 knockdown led to a significant inhibition of growth and metastasis, and induced apoptosis in PTC cells. Knockdown of NEAT1_2 significantly inhibited malignant biological behavior by downregulating the oncogene ATAD2. In addition, NEAT1_2 could act as a competing endogenous RNA to regulate the expression of ATAD2 through downregulating miR-106b-5p. Taken together, our results indicated that NEAT1_2 is overexpressed in PTC. NEAT1_2 could function as a competing endogenous RNA to regulate ATAD2 expression by sponging miR-106b-5p in PTC. Targeting NEAT1_2 could be a promising therapeutic strategy for patients with PTC.
Homocysteine (Hcy) and S-adenosylhomocysteine (AdoHcy) are critical intermediates of methionine metabolism. To investigate which, if either, of these compounds is more closely related to atherosclerosis, we fed 5 groups of apolipoprotein E (apoE)-deficient mice different diets for 8 wk to induce changes in their plasma Hcy and AdoHcy concentrations. These included an AIN-93G control diet (C), this C diet supplemented with methionine (M), the M diet deficient in folates, vitamin B-6, and vitamin B-12 (M-V), this M diet supplemented with these B vitamins (M+V), and a C diet deficient in B vitamins (C-V). Compared with controls, mice fed the C-V diet had a moderate elevation in their plasma total Hcy (tHcy) levels; however, their plasma AdoHcy concentration and atherosclerotic lesion areas were not different. In contrast, the mice fed the M+V diet had larger atherosclerotic lesion areas and elevated plasma AdoHcy concentrations but their plasma tHcy concentration did not differ from that of the group C mice. The plasma AdoHcy concentration and aortic sinus lesion areas were positively correlated (r = 0.866; P < 0.001). We observed a negative correlation between the plasma AdoHcy concentration and both the DNA methyltransferase activity (r = -0.792; P < 0.001) and global DNA methylation status (r = -0.824; P < 0.001) in the aortic tissue. Hence, our study suggests that plasma AdoHcy is a better biomarker of atherosclerosis than Hcy and may accelerate the development of atherosclerotic lesions in apoE-deficient mice that have been fed a high methionine diet. The mechanisms underlying this effect may be related to the AdoHcy-mediated inhibition of DNA methylation in the aortic tissue.
Long non-coding RNAs (lncRNAs) are emerging regulators of a diverse range of biological processes through various mechanisms. Genome-wide association studies of tumor samples have identified several lncRNAs, which act as either oncogenes or tumor suppressors in various types of cancers. Small nucleolar RNAs (snoRNAs) are predominantly found in the nucleolus and function as guide RNAs for the processing of transcription. As the host genes of snoRNAs, lncRNA small nucleolar RNA host genes (SNHGs) have been shown to be abnormally expressed in multiple cancers and can participate in cell proliferation, tumor progression, metastasis, and chemoresistance. Here, we review the biological functions and emerging mechanisms of SNHGs involved in the development and progression of endocrine-related cancers including thyroid cancer, breast cancer, pancreatic cancer, ovarian cancer and prostate cancer.
In PTC cell lines, GAS8-AS1 inhibited proliferation, activated autophagy, and increased ATG5 expression. Downregulation of ATG5 reversed GAS8-AS1-mediated activation of autophagy leading to cell death, revealing a novel mechanism of the GAS8-AS1-ATG5 axis in PTC cell lines. This provided a new experimental basis to explore the effects of lncRNA on autophagy in the treatment of thyroid cancer.
Mitochondria are the powerhouse organelles of cells; they participate in ATP generation, calcium homeostasis, oxidative stress response, and apoptosis. Thus, maintenance of mitochondrial function is critical for cellular functions. As highly dynamic organelles, the function of mitochondria is dynamically regulated by their fusion and fission in many cell types, which regulate mitochondrial morphology, number, distribution, metabolism, and biogenesis in cells. Mature rod-shaped cardiomyocytes contain thousands of end-to-end contacted spheroid mitochondria. The movement of mitochondria in these cells is limited, which hinders the impetus for research into mitochondrial dynamics in adult cardiomyocytes. In this review, we discuss the most recent progress in mitochondrial dynamics in mature (adult) cardiomyocytes and the relationship thereof with heart diseases.
The allelic frequencies of apolipoprotein E (apoE) vary substantially around the world. There is a conspicuous south-to-north gradient of e4 frequencies in Europe, with the proportion of e4 carriers from only 10-15% in the south to 40-50% in the north. The mechanism may be related to the possibility that e4 carriers are less likely to develop vitamin D deficiency. In addition, Asian populations traditionally have lower e4 frequency than Europeans, which may be attributed in part to the scarce or irregular food supplies in Western world in the recent past. However, whether these geographical distribution gradients exist in China is yet unknown. ApoE genotypes of 200 children from Nanning City were determined by PCR-restriction fragment length polymorphism (RFLP) analysis. Allele frequency data of 18 other populations were collected from published sources and correlated with latitude and longitude information from different geographic resources. In our subjects, the frequencies of apoE genotypes were E3/E3: 73.0%, E3/E2: 15.0%, E4/E3: 5.0%, E4/E4: 5.0%, and E4/E2: 2.0%; the frequencies of apoE alleles were e2: 8.5%, e3: 83.0%, and e4: 8.5%, respectively. The total sample consisted of 3,679 individuals from 19 Chinese populations; the allelic frequencies were e2: 7.6%, e3: 85.5%, and e4: 6.9%, respectively; the proportion of e4 carriers was from 4.9% in Kunming to 17.5% in Harbin. Systemic comparison among multiple Chinese populations revealed that positive correlation existed between the e4 allele frequency distribution and latitude north (r=0.586, P=0.008), but no correlation of the e4 allele frequency distribution with longitude east was found (r=-0.018, P=0.942). We conclude that there is a south-to-north, but not an east-to-west gradient for the apoE4 allele in China.
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