Piwi‐interacting RNAs (piRNAs), a novel class of small non‐coding RNAs, were first discovered in germline cells and are thought to silence transposons in spermatogenesis. Recently, piRNAs have also been identified in somatic tissues, and aberrant expression of piRNAs in tumor tissues may be implicated in carcinogenesis. However, the function of piR‐823 in colorectal cancer (CRC) remains unclear. Here, we first found that piR‐823 was significantly upregulated in CRC tissues compared with its expression in the adjacent tissues. Inhibition of piR‐823 suppressed cell proliferation, arrested the cell cycle in the G1 phase and induced cell apoptosis in CRC cell lines HCT116 and DLD‐1, whereas overexpression of piR‐823 promoted cell proliferation in normal colonic epithelial cell line FHC. Interestingly, Inhibition of piR‐823 repressed the expression of heat shock protein (HSP) 27, 60, 70. Furthermore, elevated HSPs expression partially abolished the effect of piR‐823 on cell proliferation and apoptosis. In addition, we further demonstrated that piR‐823 increased the transcriptional activity of HSF1, the common transcription factor of HSPs, by binding to HSF1 and promoting its phosphorylation at Ser326. Our study reveals that piR‐823 plays a tumor‐promoting role by upregulating phosphorylation and transcriptional activity of HSF1 and suggests piR‐823 as a potential therapeutic target for CRC.

Piwi-interacting RNAs (piRNAs), a novel class of non-coding RNAs, are enriched in germ cells and implicated in spermatogenesis. Emerging evidence demonstrated deregulated expression of piRNAs in numerous tumor types. However, changes in piRNA expression profiles in colorectal cancer (CRC) have not yet been investigated. In the present study, small RNA sequencing was used to evaluate the differences in piRNA expression profiles between CRC and adjacent non-tumor tissues, as well as to screen for differentially expressed piRNAs. The present results demonstrated that the percentage of unique piRNA reads had no notable difference between the paired CRC and adjacent non-tumor samples (0.12% vs. 0.13%); however, the counts of total piRNA reads in CRC samples were increased, compared with those in adjacent non-tumor samples (0.15% vs. 0.07%). Differential expression analysis identified 33 upregulated piRNAs and 2 downregulated piRNAs in CRC samples, among which piR-18849, piR-19521 and piR-17724 were the top three upregulated piRNAs. Reverse transcription-quantitative polymerase chain reaction further confirmed that the expression levels of piR-18849, piR-19521 and piR-17724 were increased in 80 CRC tissues, compared with paired adjacent non-tumor tissues. Furthermore, the high expression of piR-18849 and piR-19521 was associated with a poor degree of differentiation. The increased expression of piR-18849 was also associated with high lymph node metastasis. However, no associations were determined between piR-17724 expression and clinicopathological characteristics of patients. In summary, the present study is the first to provide an overview of the changes in piRNA expression patterns in CRC, shedding new light on the regulatory roles of piRNAs in colorectal carcinogenesis. piR-18849 and piR-19521 may be prognostic biomarkers for patients with CRC.

1) These compounds might contribute to the anti-hypertensive effect collectively. However, the anti-hypertensive effect of Eucommia ulmoides OLIV. bark remains largely unclear.Pharmacological studies have revealed that Eucommia ulmoides OLIV. bark extract induce endothelium and NO-cyclic guanosine monophosphate (cGMP) dependent relaxation in the rat thoracic aorta.2) Another report demonstrated that the endothelium-dependent vascular relaxation induced by the bark extract is mediated by NO and endothelium-derived hyperpolarizing factor in small vessels.3) However, the vasorelaxing components have been unclear. Recently, we found oroxylin A and wogonin isolated from Eucommia ulmoides OLIV. bark could significantly lower the perfusion pressure.4) In the previous study, we had reported that oroxylin A could relax rat thoracic aorta and it was endothelium and NO dependent.5)The present study was undertaken to investigate vasodilatory effect of wogonin and its mechanism.Wogonin ( Fig. 1) is a flavone and has a variety of cardiovascular protective effect. It could regulate migration, proliferation and apoptosis of vascular smooth muscle cells. [6][7][8] Besides, wogonin could inhibit angiogenesis, suppress collagen deposition in cardiac fibroblasts and inhibit ischemic brain injury. [9][10][11][12] There is no evidence for vascular relaxation effect of wogonin. We describe here that wogonin, unlike oroxylin A, is an endothelium-and NO-independent vasodilatory flavonoid. One report demonstrated that wogonin offered a wide margin of safety.13) It has therapeutic potential for the treatment of cardiovascular and cerebrovascular diseases.

RING finger proteins (RNFs) play a critical role in cancer initiation and progression. RNF141 is a member of RNFs family; however, its clinical significance, roles, and mechanism in colorectal cancer (CRC) remain poorly understood. Here, we examined the expression of RNF141 in 64 pairs of CRC and adjacent normal tissues by real-time PCR, Western blot, and immunohistochemical analysis. We found that there was more expression of RNF141 in CRC tissue compared with its adjacent normal tissue and high RNF141 expression associated with T stage. In vivo and in vitro functional experiments were conducted and revealed the oncogenic role of RNF141 in CRC. RNF141 knockdown suppressed proliferation, arrested the cell cycle in the G1 phase, inhibited migration, invasion and HUVEC tube formation but promoted apoptosis, whereas RNF141 overexpression exerted the opposite effects in CRC cells. The subcutaneous xenograft models showed that RNF141 knockdown reduced tumor growth, but its overexpression promoted tumor growth. Mechanistically, liquid chromatography-tandem mass spectrometry indicated RNF141 interacted with KRAS, which was confirmed by Co-immunoprecipitation, Immunofluorescence assay. Further analysis with bimolecular fluorescence complementation (BiFC) and Glutathione-S-transferase (GST) pull-down assays showed that RNF141 could directly bind to KRAS. Importantly, the upregulation of RNF141 increased GTP-bound KRAS, but its knockdown resulted in a reduction accordingly. Next, we demonstrated that RNF141 induced KRAS activation via increasing its enrichment on the plasma membrane not altering total KRAS expression, which was facilitated by the interaction with LYPLA1. Moreover, KRAS silencing partially abolished the effect of RNF141 on cell proliferation and apoptosis. In addition, our findings presented that RNF141 functioned as an oncogene by upregulating KRAS activity in a manner of promoting KRAS enrichment on the plasma membrane in CRC.

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