The Clinical Significance and Expression Level of miR-411-5p in Colorectal Cancer.

Background: MicroRNAs (miRNAs) have been widely recognized as crucial regulators in the development and progression of various cancers, including colorectal cancer (CRC). Previous studies have highlighted the involvement of several miRNAs in CRC, such as miR-145, miR-29a-3p, and miR-196. However, the specific role and clinical significance of miR-411-5p in CRC have not been thoroughly investigated, representing a significant gap in the current understanding of CRC biology. While miR-411-5p has been implicated in the pathogenesis of other human malignancies, its precise mechanisms and impact on CRC development and prognosis remain largely unexplored. Understanding the functional relevance of miR-411-5p in CRC and elucidating its molecular interactions can provide valuable insights into the underlying mechanisms of CRC progression and potentially identify novel therapeutic targets. Therefore, this study aims to investigate the clinical value and level of miR-411-5p in colorectal cancer, shedding light on its potential as a diagnostic and prognostic biomarker. Additionally, we aim to explore the molecular mechanisms underlying the effects of miR-411-5p on CRC cells, particularly its interaction with the target gene NFE2L3. By filling this knowledge gap, our research contributes to a deeper understanding of the role of miR-411-5p in CRC and opens avenues for developing targeted therapies for this prevalent malignancy. Methods: Colorectal cancer (CRC) tissue samples and corresponding normal paracancerous tissue samples were collected from 60 CRC patients treated at the Affiliated Hospital of Hebei University. Normal paracancerous tissue refers to the healthy tissue adjacent to the cancerous region. These tissue samples were obtained through biopsies, and the patients provided informed consent for their use in the study. To investigate the expression levels of miR-411-5p and NFE2L3, we employed quantitative reverse transcription polymerase chain reaction (qRT-PCR) analysis. This technique allowed us to measure the levels of miR-411-5p and NFE2L3 mRNA in both CRC and normal tissue samples. Additionally, we validated the protein levels of NFE2L3 using Western blot analysis. Furthermore, we assessed the functional impact of miR-411-5p on CRC cells through various assays. The MTT assay determined cell viability, the transwell migration assay evaluated cell migration and invasion abilities, and flow cytometry measured the rate of apoptosis in CRC cells. To confirm the molecular interaction between miR-411-5p and its target gene NFE2L3, we conducted dual-luciferase reporter assays. These assays enabled us to validate the binding between miR-411-5p and the 3' untranslated region (3'UTR) of the NFE2L3 mRNA. To investigate the potential therapeutic role of NFE2L3 in CRC, we transfected CRC cells with pcDNA3.0-NFE2L3, a plasmid overexpressing NFE2L3. This allowed us to assess the impact of NFE2L3 restoration on the behavior of CRC cells. Results: Overexpression of miR-411-5p in CRC cells significantly reduced cell viability, inhibited migration and invasion, and increased the rate of apoptosis. Conversely, inhibition of miR-411-5p expression exerted the opposite effects on the biological behavior of CRC cells. Furthermore, our study revealed that NFE2L3 is a downstream target of miR-411-5p. Dual-luciferase reporter assays confirmed the binding between miR-411-5p and the 3'UTR of NFE2L3 mRNA, indicating a direct interaction between them. To investigate the therapeutic potential of targeting NFE2L3 in CRC, we transfected CRC cells with pcDNA3.0-NFE2L3, resulting in the restoration of NFE2L3 levels. This restoration effectively reversed the effects induced by miR-411-5p mimics on the behavior of CRC cells. Conclusion: Our study provides compelling evidence for the tumor-suppressive role of miR-411-5p in CRC. The overexpression of miR-411-5p resulted in reduced cell viability, inhibited migration and invasion, and increased apoptosis in CRC cells. Importantly, we identified NFE2L3 as a downstream target of miR-411-5p and demonstrated its involvement in mediating the effects of miR-411-5p on CRC cell behavior. These findings not only confirm the tumor-suppressive role of miR-411-5p in CRC but also highlight NFE2L3 as a promising target for novel therapeutic strategies. Targeting NFE2L3 to modulate the biological function of CRC cells may hold therapeutic potential and serve as a basis for the development of targeted drugs. Further investigations are warranted to fully elucidate the underlying molecular mechanisms of miR-411-5p-NFE2L3 interaction and its impact on CRC progression. Additionally, future studies could explore the clinical implications of miR-411-5p as a diagnostic or prognostic biomarker in CRC patients. By advancing our understanding of the intricate regulatory networks involved in CRC, we can pave the way for personalized therapeutic approaches and improve patient outcomes.

Protein Phosphatase PPM1B Inhibits Gastric Cancer Progression and Serves as a Favorable Prognostic Biomarker.

BACKGROUND: Protein phosphatase PPM1B, also named as PP2Cß, is a member of serine/threonine phosphatase family. Dysregulated expression of PPM1B has been reported in several malignancies; nevertheless, its role in gastric cancer remains unknown. Here, we aimed to initially investigate the expression and function of PPM1B in gastric adenocarcinoma. METHODS: We firstly evaluated the protein expression of PPM1B in our enrolled retrospective cohort (n=161) via immunohistochemistry staining. Univariate and multivariate analyses were conducted to assess its prognostic value. Cellular experiments and xenografts in mice model were also performed to validate the role of PPM1B in gastric adenocarcinoma progression. RESULTS: The advanced tumor stage was characterized with a lower PPM1B level. Lower PPM1B was associated with poor prognosis in both The Cancer Genome Atlas (TCGA) dataset and our cohort (P<0.05). Furthermore, Cox regression analysis demonstrated that PPM1B was a novel independent prognostic factor for gastric adenocarcinoma patients (hazard ratio=0.35, P=0.001). Finally, cellular and xenografts data confirmed that overexpressing PPM1B can remarkably attenuated gastric adenocarcinoma growth. CONCLUSION: Low expression of PPM1B may be a potential molecular marker for poor prognosis in gastric adenocarcinoma.

Effect of KNL1 on the proliferation and apoptosis of colorectal cancer cells.

OBJECTIVE: To identify the expression of kinetochore scaffold 1 (KNL1) in colorectal tumor tissues and to clarify the role of this gene in the proliferation capability of colorectal cancer cells. METHODS: A total of 108 paired colorectal tumor and normal tissue samples were collected from patients with colorectal cancer and subjected to quantitative polymerase chain reaction and immunohistochemistry analyses. Expression levels of KNL1 mRNA and protein were compared between tumor and normal tissues, and KNL1 levels were evaluated in relation to the patients' tumor differentiation, sex, lymph node metastasis, TNM stage, infiltration depth, age, and tumor location. Survival curves were also constructed and compared between patients with tumor samples with and without KLN1 protein expression. KNL1 was under-expressed in colorectal cancer cells in vitro using lentiviral transfection with short hairpin RNA, and its function was evaluated by proliferation, colony-formation, and apoptosis assays. Expression levels of BUB1 protein were also compared between tumor and normal tissues, and the correlation between KNL1 expression and BUB1 expression in colorectal cancer tissues was examined. RESULTS: KNL1 mRNA and protein were both highly expressed in colorectal tumor tissues compared with paired normal tissues. KNL1 downregulation significantly inhibited colorectal cancer cell proliferation and colony formation, and promoted apoptosis. KNL1 protein expression was significantly associated with tumor differentiation, but not with sex, lymph node metastasis, TNM stage, infiltration depth, age, or tumor location. KNL1 protein expression was also significantly associated with poorer survival. Moreover, there was a significant correlation between KNL1 and BUB1 in colorectal cancer tissues. CONCLUSIONS: KNL1 plays an effective role in decreasing apoptosis and promoting the proliferation of colorectal cancer cells, suggesting that its inhibition may represent a promising therapeutic approach in patients with colorectal cancer.