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BackgroundResistance to radiation therapy is still a challenge for treatment of pancreatic cancer(PC). Long non-coding RNAs (lncRNA) HOTAIR has been found to play a oncogenic role in several cancers. However, the correlation between HOTAIR and radiotherapy in PC is still unclear.MethodsTCGA data was collected to analyze the expression of HOTAIR and its relationship with PC progression. A series of functional experiments were conducted to explore the role of HOTAIR in PC radiosensitivity and its underlying molecular mechanisms.ResultsBy the analysis of the TCGA data, we found HOTAIR expression in PC tissues was significantly higher than normal tissues and associated with tumor progression. The function analysis showed HOTAIR was enriched in biological regulation and response to stimulus. And in vitro study, the expression of HOTAIR was increased in PANC-1 and AsPC-1 cells after radiation. We identified that HOTAIR knockdown could enhance radiosensitivity and influence autophagy by up-regulating ATG7 expression in PC cells. By futher rescue experiments using rapamycin, activation of autophagy could reversed the the inhibition of cell proliferation and colony formation, as well as promotion of apoptosis mediated by HOTAIR knockdown, indicating that HOTAIR knockdown promoted radiosensitivity of PC cells by regulating autophagy.ConclusionOur finding revealed the the regulatory role of HOTAIR in radiosensitivity and provided a a new sight to improve radiotherapy effciency in PC.

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Our findings indicate that upregulated SERPINE2 may contribute to the aggressive phenotype of gastric cancer and suggest that SERPINE2 can be used as a novel prognostic factor and anticancer target in patients with gastric cancer.

Although the expression pattern and biological functions of ataxia-telangiectasia group D complementing gene (ATDC) had been implicated in several types of cancer, the roles and potential mechanisms of ATDC in lung cancer cell invasion are still ambiguous. In this study, we used gain- and loss-of-function analyses to explore the roles and potential mechanisms of ATDC in lung cancer cell invasion. siRNA knockdown of ATDC impaired cell invasion in A549 and H1299 cell lines, and its overexpression promoted cell invasion in HBE cell line. ATDC may contribute to the invasive ability of lung cancer cells by promoting the expression of invasion-related matrix metalloproteinase 9 (MMP-9). In addition, ATDC increased activating protein 1 (AP-1) reporter luciferase activity and the protein and mRNA levels of c-Jun and c-Fos. We further demonstrated that the roles of ATDC on cell invasion, MMP-9 upregulation, and AP-1 activation were dependent on extracellular signal-regulated protein kinase (ERK) and c-Jun N-terminal kinase (JNK) pathway activation, and ERK inhibitor U0126 or JNK inhibitor SP600125 blocked these effects of ATDC. These results suggested that ATDC upregulates MMP-9 to promote lung cancer cell invasion by activating ERK and JNK pathways.

The deposition of intramuscular (IM) and subcutaneous (SC) fat is an important trait influencing pork quality. Understanding the genetic differences between these two types of adipose tissues is consequently of great importance for pig breeding. Here, we established primary cultures of IM and SC adipocytes from Jiaxing black pigs. The microRNA (miRNA) expression profiles of the two types of adipocytes were obtained by RNA-seq. A total of 741 miRNAs were identified in IM and SC adipocytes, including 155 significant differentially expressed (SDE) miRNAs. According to gene ontology and Kyoto Encyclopedia of Genes analysis, the target genes of the SDE miRNAs were enriched in categories and pathways related to transcriptional regulation, fatty acid biosynthesis, as well as the MAPK and PI3K/Akt pathways. Notably, miR-206 expression was 36-fold higher in IM adipocytes than in SC adipocytes. The overexpression of miR-206 in IM and SC adipocytes decreased cell proliferation and triglyceride accumulation. Luciferase activity assays and quantitative polymerase chain reaction confirmed that miR-206 regulates adipocyte proliferation by targeting STARD7 and inhibits adipogenesis by repressing Krüppel-like factor 4 (KLF4) expression. Accordingly, the effect of miR-206 mimics was attenuated by the overexpression of KLF4 in adipocytes. Taken together, we identified the expression profiles of miRNAs in adipocytes, which revealed that miR-206 acts as a suppressor of adipogenesis.

Increasing intramuscular (IM) fat while concomitantly decreasing subcutaneous (SC) fat content is one major goal of pig breeding. Identifying genes involved in lipid metabolism is critical for this goal. Galectin-12 (LGALS12) has been proven to be an important regulator of fat deposition in mouse models; however, the effect and regulatory mechanisms of LGALS12 on porcine adipogenesis are still unknown. In this study, the effects of LGALS12 on fat deposition were explored with primary culture of porcine SC and IM adipocytes. Analysis of LGALS12 expression across different tissues revealed that LGALS12 was predominantly expressed in adipose tissue. The LGALS12 expression patterns across stages of adipocyte differentiation were also evaluated, with differences observed between SC and IM fat. Small interfering RNA (siRNA) of LGALS12 was designed and transfected into porcine adipocytes derived from SC and IM fat. After transfection, the expression level of LGALS12 was significantly reduced, and the number of lipid droplets was reduced in adipocytes from both SC and IM fat. Simultaneously, the levels of adipogenic markers, including PPARγ and aP2, were decreased, whereas hydrolysis markers, including adipose triglyceride lipase (ATGL) and hormone-sensitive lipase (HSL), were increased. Furthermore, the activation of lipolysis signals, such as the phosphorylation of PKA and Erk1/2, were observed with LGALS12 knockdown in terminally differentiated adipocytes from both SC and IM sources. Taken together, these results suggest that LGALS12 knockdown can inhibit adipogenesis of porcine adipocytes by downregulating lipogenic genes and activating the PKA-Erk1/2 signaling pathway.

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