Although PIWI-interacting RNAs (piRNAs) have recently been linked to human diseases, their roles and functions in malignancies remain unclear. This study aimed to investigate the significance of some piRNAs in colorectal cancer (CRC).Methods: We first analyzed the expression profile of piRNAs in CRC using the TCGA and GEO databases. The top 20 highly expressed piRNAs were selected and tested in our CRC tumor and non-tumor tissue samples. We then examined the relevance of the significantly differentially expressed piRNA to the CRC outcomes in 218 patients receiving postoperative chemotherapy and 317 patients receiving neoadjuvant chemotherapy. A series of biochemical and molecular biological assays were conducted to elucidate the functional mechanism of a piRNA of interest in CRC. Furthermore, experiments with mice xenografts were performed to evaluate the therapeutic effect of an inhibitor specific to the piRNA.Results: We found that among the examined 20 piRNAs, only piRNA-54265 was overexpressed in CRC compared with non-tumor tissues and higher levels in tumor or in serum were significantly associated with poor survival in patients. Functional assays demonstrated that piRNA-54265 binds PIWIL2 protein and this is necessary for the formation of PIWIL2/STAT3/phosphorylated-SRC (p-SRC) complex, which activates STAT3 signaling and promotes proliferation, metastasis and chemoresistance of CRC cells. Treatment with a piRNA-54265 inhibitor significantly suppressed the growth and metastasis of implanted tumors in mice.Conclusion: These results indicate that piRNA-54265 is an oncogenic RNA in CRC and thus might be a therapeutic target.
The findings of the present study demonstrate that expression of mutant CASQ2(D307H) in the mouse heart results in abnormal myocyte Ca2+ handling and predisposes to complex ventricular arrhythmias similar to the CPVT phenotype observed in human patients.
BACKGROUND
As one effective treatment for lateral pelvic lymph node (LPLN) metastasis (LPNM), laparoscopic LPLN dissection (LPND) is limited due to the complicated anatomy of the pelvic sidewall and various complications after surgery. With regard to improving the accuracy and completeness of LPND as well as safety, we tried an innovative method using indocyanine green (ICG) visualized with a near-infrared (NIR) camera system to guide the detection of LPLNs in patients with middle-low rectal cancer.
AIM
To investigate whether ICG-enhanced NIR fluorescence-guided imaging is a better technique for LPND in patients with rectal cancer.
METHODS
A total of 42 middle-low rectal cancer patients with clinical LPNM who underwent total mesorectal excision (TME) and LPND between October 2017 and March 2019 at our institution were assessed and divided into an ICG group and a non-ICG group. Clinical characteristics, operative outcomes, pathological outcomes, and postoperative complication information were compared and analysed between the two groups.
RESULTS
Compared to the non-ICG group, the ICG group had significantly lower intraoperative blood loss (55.8 ± 37.5 mL
vs
108.0 ± 52.7 mL,
P
= 0.003) and a significantly larger number of LPLNs harvested (11.5 ± 5.9
vs
7.1 ± 4.8,
P
= 0.017). The LPLNs of two patients in the non-IVG group were residual during LPND. In addition, no significant difference was found in terms of LPND, LPNM, operative time, conversion to laparotomy, preoperative complication, or hospital stay (
P
> 0.05).
CONCLUSION
ICG-enhanced NIR fluorescence-guided imaging could be a feasible and convenient technique to guide LPND because it could bring specific advantages regarding the accuracy and completeness of surgery as well as safety.
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