ChiCTR-RRC-17014152.

MicroRNAs (miR) are important in various crucial cell processes including proliferation, migration and invasion. Dysregulation of miRNAs have been increasingly reported to contribute to colorectal cancer. However, the detailed biological function and potential mechanisms of miR‑1273g‑3p in colorectal cancer remain poorly understood. The expression levels of miR‑1273g‑3p in human colorectal cancer LoVo cell lines were detected via reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR). The target genes of miR‑1273g‑3p were predicted by bioinformatics and verified by a luciferase reporter assay, RT‑qPCR and western blotting. The MTT, wound‑healing and Transwell assays were used to examine the biological functions of miR‑1273g‑3p in LoVo cells. The potential molecular mechanisms of miR‑1273g‑3p on LoVo cell proliferation, migration and invasion was detected by western blotting. The results of the present study demonstrated that miR‑1273g‑3p expression was extensively upregulated in LoVo cells compared with the normal colon epithelial NCM460 cell line. Further studies indicated that miR‑1273g‑3p inhibitor significantly suppressed LoVo cell proliferation, migration and invasion compared with inhibitor control. Following this, the cannabinoid receptor 1 (CNR1) was identified as a direct target gene of miR‑1273g‑3p. Knockdown of CNR1 restored the phenotypes of LoVo cells transfected with miR‑1273g‑3p inhibitor. Furthermore, the potential molecular mechanism of miR‑1273g‑3p on LoVo cell proliferation, migration and invasion may be mediated by activating the Erb‑B2 receptor tyrosine kinase 4 (ERBB4)/phosphoinositide‑3‑kinase regulatory subunit 3 (PIK3R3)/mechanistic target of rapamycin (mTOR)/S6 kinase 2 (S6K2) signaling pathway. These observations indicated that miR‑1273g‑3p promoted the proliferation, migration and invasion of LoVo cells via CNR1, and this may have occurred through activation of the ERBB4/PIK3R3/mTOR/S6K2 signaling pathway, suggesting that miR‑1273g‑3p may serve as a novel therapeutic target for the effective treatment of colorectal cancer.

BackgroundHER2-positive breast cancer was aggressive, resulting in a poorer prognosis. This multicenter study analyzed the real-world data of women treated with pyrotinib-based therapy, aiming to describe their characteristics, treatment regimens, and to investigate the clinical outcomes.MethodsA total of 141 patients with HER2-positive breast cancer were enrolled from February 2019 to April 2020. Last follow-up time was February 2021. All patients were treated with pyrotinib-based therapy in 21-day cycles. The primary endpoint was progression-free survival (PFS).ResultsThe median PFS (mPFS) for pyrotinib-based therapy was 12.0 months (95%CI 8.1-17.8) in all patients. Among the patients with liver metastases, mPFS was 8.7 months (95%CI, 6.3-15.4) compared to 12.3 months (95%CI, 8.8-23.3) for patients without liver metastases (P=0.172). In addition, patients receiving pyrotinib-based therapy as their >2 lines treatment had a numerically lower mPFS than those receiving pyrotinib-based therapy as their ≤2 lines treatment [8.4 (95%CI, 5.9-15.4) vs. 15.1 (95%CI, 9.3-22.9) months, P=0.107]. The mPFS was 12.2 months (95%CI, 7.9-18.8) in patients with previous exposure to trastuzumab and 11.8 months (95%CI, 6.8-22.9) in patients without previous exposure to trastuzumab (P=0.732). Moreover, mPFS in patients receiving regimens with and without capecitabine were 15.1 months (95%CI, 10.0-18.8) and 8.4 months (95%CI, 6.7-22.9), respectively (P=0.070). Furthermore, in patients with brain metastases, estimated 6-month PFS rate was 70.0%, and rate at 12 months was 60.0%. Seventy patients with measurable lesions were evaluable for response. The objective response rate was 38.6% and disease control rate was 85.7%. The most common adverse event was diarrhea (85.0%).ConclusionPyrotinib-based therapy showed promising efficacy in patients with HER2-positive breast cancer and was well tolerated, especially in patients treated with pyrotinib as ≤2 lines treatment and receiving regimens with capecitabine. The results of this real-world study further confirmed the intriguing efficacy of pyrotinib.