MiR-363 restrain the proliferation, migration and invasion of colorectal carcinoma cell by targeting E2F3.

MicroRNA (miRNA) is associated with tumor cell proliferation, migration and invasion. Studies have shown that miRNAs are closely related to the occurrence and development of colorectal cancer (CRC), but the mechanisms deserve further investigation. In this study, we aim to explore the role of miR-363 on CRC tumorigenesis. Using CRC cell lines, we tested the expression of miR-363 by using RT-PCR, and miR-363 effect on cell behavior was test by using CCK-8 assay, wound-healing assay and cell invasion assay, and western blotting. Luciferase reporter assay and western blot confirmed that E2F3 was the target gene for miR-363. We further examined the effect of E2F3 on the regulation of miR-363 on cell behavior through knockdown of E2F3. Western blot and RT-PCR assay showed that miR-363 inhibited the expression of E2F3 in HCT-116 and SW480 cell. MiR-363 overexpression or E2F3 knockdown inhibited cell proliferation, migration and invasion of CRC. This study demonstrated that miR-363 is able to suppress cell proliferation, migration and invasion by negative regulating E2F3 in CRC cells, and inhibits tumor growth in vivo.

Corrigendum: STAT5a Confers Doxorubicin Resistance to Breast Cancer by Regulating ABCB1.

[This corrects the article DOI: 10.3389/fonc.2021.697950.].

CRNDE silencing promotes apoptosis and enhances cisplatin sensitivity of colorectal carcinoma cells by inhibiting the Akt/mTORC1-mediated Warburg effect.

Colorectal cancer (CRC) is one of the most prevalent gastrointestinal tumors worldwide, with a high mortality rate. The lncRNA colorectal neoplasia differentially expressed (CRNDE) is upregulated in CRC and is involved in regulating the apoptosis, proliferation, and drug sensitivity of CRC cells. However, the specific underlying mechanisms remain to be elucidated. The aim of the present study was to investigate the effects of CRNDE on the Warburg effect in CRC cells, as well as the associated mechanisms. The expression of CRNDE in HCT-116 cells was overexpressed or silenced by transfection. Apoptosis, cisplatin sensitivity, the Warburg effect, and Akt/mTOR activation were evaluated. The results demonstrated that CRNDE inhibition decreased the proliferation and increased the apoptosis and cisplatin sensitivity of HCT-116 cells. In addition, CRNDE inhibition attenuated the Warburg effect in HCT-116 cells, as verified by a decrease in ATP production, lactic acid levels, glucose uptake, and the expression of Warburg effect-related enzymes (GLUT1, LDHA, HK2, and PKM2). CRNDE inhibition also suppressed the activity of the Akt/mTORC1 pathway, as demonstrated by the decreased phosphorylation of Akt, S6K, S6, and mTOR and the increased phosphorylation of 4EBP-1 and EIF-4E. The CRNDE overexpression-induced increase in ATP and lactic acid levels and glucose uptake in HCT-116 cells was reversed by Akt and mTOR inhibitors. These findings indicate that CRNDE silencing promotes apoptosis and enhances cisplatin sensitivity in colorectal carcinoma cells, which may be mediated by the regulation of the Warburg effect via the Akt/mTORC1 pathway. The present study thus provides a potential strategy for the treatment of CRC.

STAT5a Confers Doxorubicin Resistance to Breast Cancer by Regulating ABCB1.

Chemoresistance is a daunting challenge to the prognosis of patients with breast cancer. Signal transducer and activator of transcription (STAT) 5a plays vital roles in the development of various cancers, but its function in breast cancer is controversial, and its role in chemoresistance in breast cancer remains unexplored. Here we identified STAT5a as a chemoresistance inducer that regulates the expression of ABCB1 in breast cancer and can be targeted by pimozide, an FDA-approved psychotropic drug. First, we found that STAT5a and ABCB1 were expressed at higher levels in doxorubicin-resistant cell lines and chemoresistant patients, and their expression was positively correlated. Then, we confirmed the essential roles of STAT5a and ABCB1 in doxorubicin resistance in breast cancer cells and the regulation of ABCB1 transcription by STAT5a. Subsequently, the efficacy of pimozide in inhibiting STAT5a and sensitizing doxorubicin-resistant breast cancer cells was tested. Finally, we verified the role of STAT5a in doxorubicin resistance in breast cancer and the efficacy of pimozide in reversing this resistance in vivo. Our study demonstrated the vital role of STAT5a in doxorubicin resistance in breast cancer. Targeting STAT5a might be a promising strategy for treating doxorubicin-resistant breast cancer. Moreover, repurposing pimozide for doxorubicin resensitization is attractive due to the safety profile of pimozide.