MiR-372-3p promotes tumor progression by targeting LATS2 in colorectal cancer.

OBJECTIVE: Many studies suggest that microRNAs can promote the malignant development of tumors. MiRNA-372-3p (miR-372-3p) has been proved to be associated with a variety of cancers. However, the role of miR-372-3p in colorectal cancer (CRC) is unclear. PATIENTS AND METHODS: We analyzed the expression of miR-372-3p in CRC tissues and several CRC cell lines by quantitative Real Time-PCR. The relationship between miR-372-3p and clinical pathology was also analyzed in CRC patients. Kaplan-Meier analysis and Cox multivariate analysis were used to evaluate the prognostic significance of miR-372-3p in CRC. Next, we investigated the biological function of miR-372-3p, including cell proliferation, migration, and invasion and analyzed its potential molecular mechanism in vivo and in vitro. RESULTS: Our data showed that the expression of miR-372-3p was dramatically increased in CRC tissues compared with normal tissues. Moreover, the high expression of miR-372-3p was significantly correlated with tumor size and differentiation. Kaplan-Meier analysis showed that the high miR-372-3p expression group patients had a significantly shorter recurrence-free survival (RFS) and disease-specific survival (DSS) than those with the low miR-372-3p group. The analysis of the prognostic factors revealed that miR-372-3p was an independent prognostic factor for RFS and DSS in CRC patients. The knockdown of miR-372-3p inhibited the proliferation, migration, and invasion in HCT116 and SW480 cells. Interestingly, the overexpression of LATS2 partially reversed the miR-372-3p -mediated cell proliferation, migration, and invasion of CRC. Besides, the Hippo signaling pathway was demonstrated to be activated by decreasing of miR-372-3p in CRC. Thus, our study revealed that miR-372-3p is involved in CRC progression by inhibiting the Hippo signaling pathway through its target LATS2. MiR-372-3p and its target genes with signaling pathways are new hope for precise treatment of CRC. CONCLUSIONS: The upregulation of miR-372-3p was involved in the process of CRC progression by inhibiting the Hippo signaling pathway through inhibition of LATS2. We showed that miR-372-3p and its target genes with signaling pathways are a novel hope for precise treatment of CRC.

[Studies on nimodipine sustained-release tablet capable of floating on gastric fluid with prolonged gastric resident time].

Nimodipine was incorporated into poloxamer 188 solid dispersion before formulation, then mixed excipient and solid dispersion were directly compressed into nimodipine floating sustained-release tablet(NM-FSRT). Formulations were optimized using uniform design and variables affecting nimodipine release from matrix were studied. Preliminary in vivo evaluation was carried out in healthy volunteers. Results showed that the optimized formulation could remain floating on gastric fluid for over 10 hours. In vitro release(0.15-6 h) conformed to zero-order kinetics. Hydroxypropylmethylcellulose(HPMC) and polyethylene glycol 6000(PEG 6000) showed the biggest effect on in vitro drug release. Increasing HPMC content and decreasing PEG 6000 content led to decrease of nimodipine release in vitro. NM-FSRT did remain floating on gastric fluid with prolonged gastric resident time(GRT) of 5 hours under fed condition, while GRT was only 3 hours under fasted condition. GRT of nimodipine conventional tablet(NM-CT) under fed and fasted conditions was 3 and 2 hours, respectively. Relative bioavailability of NM-FSRT was 391.46% and MRT was over twice that of NM-CT. NM-FSRT appeared to have prolonged GRT and improved bioavailability.