Long non-coding RNAs (lncRNAs) play key roles in human cancers. Here, FEZF1-AS1, a highly overexpressed lncRNA in colorectal cancer, was identified by lncRNA microarrays. We aimed to explore the roles and possible molecular mechanisms of FEZF1-AS1 in colorectal cancer. LncRNA expression in colorectal cancer tissues was measured by lncRNA microarray and qRT-PCR. The functional roles of FEZF1-AS1 in colorectal cancer were demonstrated by a series of and experiments. RNA pull-down, RNA immunoprecipitation and luciferase analyses were used to demonstrate the potential mechanisms of FEZF1-AS1. We identified a series of differentially expressed lncRNAs in colorectal cancer using lncRNA microarrays, and revealed that FEZF1-AS1 is one of the most overexpressed. Further validation in two expanded colorectal cancer cohorts confirmed the upregulation of FEZF1-AS1 in colorectal cancer, and revealed that increased FEZF1-AS1 expression is associated with poor survival. Functional assays revealed that FEZF1-AS1 promotes colorectal cancer cell proliferation and metastasis. Mechanistically, FEZF1-AS1 could bind and increase the stability of the pyruvate kinase 2 (PKM2) protein, resulting in increased cytoplasmic and nuclear PKM2 levels. Increased cytoplasmic PKM2 promoted pyruvate kinase activity and lactate production (aerobic glycolysis), whereas FEZF1-AS1-induced nuclear PKM2 upregulation further activated STAT3 signaling. In addition, PKM2 was upregulated in colorectal cancer tissues and correlated with FEZF1-AS1 expression and patient survival. Together, these data provide mechanistic insights into the regulation of FEZF1-AS1 on both STAT3 signaling and glycolysis by binding PKM2 and increasing its stability. .

The incidence and death rate of colorectal cancer ( CRC ) is very high, which brings great need to understand the early molecular events of CRC . These studies demonstrate that long noncoding RNA (lnc RNA ) plays an important role in the occurrence and development of human cancer. Small nucleolar RNA host gene 15 ( SNHG 15) was recently identified as a cancer‐related lnc RNA . In this study, we aimed to evaluate the function and mechanism of SNHG 15 in CRC . The expression of SNHG 15 was detected by quantitative RT ‐ PCR ( qRT ‐ PCR ) in CRC tissues and matched noncancerous tissues ( NCT s). CCK ‐8 assay, colony formation assay, flow cytometric analysis, and nude mouse xenograft mode were used to examine the tumor‐promoting function of SNHG 15 in vitro and in vivo. The binding relationship between SNHG 15, miR‐338‐3p and the target genes of miR‐338‐3p were screened and identified by databases, qRT ‐ PCR , dual luciferase reporter assay and western blot. Our results showed that SNHG 15 was up‐regulated in CRC tissues compared with paired NCT s ( P < 0.0001). High level of SNHG 15 expression predicted poor prognosis of CRC ( P = 0.0051). SNHG 15 overexpression could promote cell proliferation and inhibit cell apoptosis. Animal experiments showed that up‐regulation of SNHG 15 promoted tumor growth in vivo. The results of mechanism experiments showed that SNHG 15 could bind to miR‐338‐3p and block its inhibition on the expression and activity of FOS or RAB 14. In conclusion SNHG 15 promotes cell proliferation through SNHG 15/miR‐338‐3p/ FOS ‐ RAB 14 axis in CRC.

The transcription factor HNF4α (hepatocyte nuclear factor-4α) is required for increased β-cell proliferation during metabolic stress in vivo. We hypothesized that HNF4α could induce proliferation of human β-cells. We employed adenoviral-mediated overexpression of an isoform of HNF4α (HNF4α8) alone, or in combination with cyclin-dependent kinase (Cdk)6 and Cyclin D3, in human islets. Heightened HNF4α8 expression led to a 300-fold increase in the number of β-cells in early S-phase. When we overexpressed HNF4α8 together with Cdk6 and Cyclin D3, β-cell cycle entry was increased even further. However, the punctate manner of bromodeoxyuridine incorporation into HNF4α(High) β-cells indicated an uncoupling of the mechanisms that control the concise timing and execution of each cell cycle phase. Indeed, in HNF4α8-induced bromodeoxyuridine(+,punctate) β-cells we observed signs of dysregulated DNA synthesis, cell cycle arrest, and activation of a double stranded DNA damage-associated cell cycle checkpoint mechanism, leading to the initiation of loss of β-cell lineage fidelity. However, a substantial proportion of β-cells stimulated to enter the cell cycle by Cdk6 and Cyclin D3 alone also exhibited a DNA damage response. HNF4α8 is a mitogenic signal in the human β-cell but is not sufficient for completion of the cell cycle. The DNA damage response is a barrier to efficient β-cell proliferation in vitro, and we suggest its evaluation in all attempts to stimulate β-cell replication as an approach to diabetes treatment.

There has been no report on enzyme-controlled disassembly of self-quenched NIR fluorescent nanoparticles turning fluorescence on for specific detection/imaging of the enzyme's activity in vitro and in vivo. Herein, we reported the rational design of new NIR probe 1 whose fluorescence signal was self-quenched upon reduction-controlled condensation and subsequent assembly of its nanoparticles (i.e., 1-NPs). Then disassembly of 1-NPs by furin turned the fluorescence on. Employing this enzymatic strategy, we successfully applied 1-NPs for NIR detection of furin in vitro and NIR imaging furin activity in living cells. Moreover, we also applied 1-NPs for discriminative NIR imaging of MDA-MB-468 tumors in nude mice. This NIR probe 1 might be further developed for tumor-targeted imaging in routine preclinical studies or even in patients in the future.