<p>Downregulation of miR-575 Inhibits the Tumorigenesis of Gallbladder Cancer via Targeting p27 Kip1</p>

Abstract

Background: Gallbladder cancer (GBC) is the most common biliary tract malignant cancer worldwide. It has been reported that microRNA-575 (miR-575) was involved in the tumorigenesis of many cancers. However, the role of miR-575 during the progression of GBC remains largely unknown. Methods: The expression of miR-575 in GBC cells was detected by quantitative real-time polymerase chain reaction. The proliferation of GBC cells was examined by CCK-8 assay and Ki-67 staining. Apoptosis of GBC cells was measured by flow cytometry, and cell invasion was tested by transwell assay. Moreover, protein expressions in GBC cells were evaluated using Western blot. The target gene of miR-575 was predicted using Targetscan and miRDB. Finally, xenograft tumor model was established to verify the function of miR-575 in GBC in vivo. Results: Our findings indicated that miR-575 antagonist decreased the proliferation and invasion of GBC cells. In addition, miR-575 antagonist significantly induced apoptosis of GBC cells via inducing G1 arrest. Meanwhile, p27 Kip1 was found to be a direct target of miR-575 with luciferase reporter assay. Moreover, miR-575 antagonist significantly decreased the expressions of CDK1 and cyclin E1 and upregulated the levels of cleaved caspase3 and p27 Kip1 in GBC cells. Finally, miR-575 antagonist notably suppressed GBC tumor growth in vivo. Conclusion: Downregulation of miR-575 significantly inhibited the tumorigenesis of GBC via targeting p27 Kip1. Thus, miR-575 might be a potential novel target for the treatment of GBC.

DRP1 contributes to head and neck cancer progression and induces glycolysis through modulated FOXM1/MMP12 axis

“…Abnormal expression of miR-575 may lead to cancer development. Previous studies indicated that miR-575 plays an oncogenic role in promoting cell proliferation, migration and invasion in NSCLC, HCC and gallbladder cancer [22,43,44]. In contradiction to these results, miR-575 overexpression FOXM1 is a transcriptional factor that plays a pivotal role in cancer development.…”

“…Abnormal expression of miR‐575 may lead to cancer development. Previous studies indicated that miR‐575 plays an oncogenic role in promoting cell proliferation, migration and invasion in NSCLC, HCC and gallbladder cancer [22,43,44]. In contradiction to these results, miR‐575 overexpression significantly inhibited migration, proliferation and angiogenesis as well as induction of apoptosis of HUVEC by targeting the Rab5/MEK pathway, indicating that miR‐575 plays a tumor suppressor role in HUVEC [45].…”

LncRNA RPL34-AS1 suppresses the proliferation, migration and invasion of esophageal squamous cell carcinoma via targeting miR-575/ACAA2 axis

“…MiR-575 increased proliferation and inhibited apoptotic death of gastric cancer cells by regulating PTEN both in vitro and vivo [ 36 ]. Knockdown of miR-575 significantly suppressed proliferation and invasion of gallbladder cancer (GBC) cells via targeting p27 Kip1 [ 37 ]. Overexpression of lncRNA MIR31HG decreased the expression of miR-575 by targeting ST7L, which acted as a tumor suppressor in hepatocellular carcinoma [ 38 ].…”

Development of a MicroRNA Signature Predictive of Recurrence and Survival in Pancreatic Ductal Adenocarcinoma

“…Our findings are consistent with miR-181b/d potentially having tumor suppressive roles in PDAC. Although miR-575 has not been previously linked to PDAC, it has been implicated in development of other gastrointestinal cancers, such as gastric cancer via inhibition of PTEN [25], biliary cancer via inhibition of p27Kip1 [26], and hepatocellular carcinoma via inhibition of ST7L [27]. Interestingly, in our study, miR-575 decreased expression was associated with higher risk score and recurrence; it is possible that miR-575 may have disparate tissue-specific functions and that its downregulation is secondary to upregulation of other pathways that mediate PDAC recurrence.…”