Insight into the effects of microRNA‑23a‑3p on pancreatic cancer and its underlying molecular mechanism

Chao, Jiadeng; Zhang, Xudong; Ding, Dong; Wu, Si-Pei; Ma, Le; Zhu, Bei; Shan, Shiting; Xiao, Yun; Gao, Peng; Li, Jun; Zhu, Chen; Qin, Xihu

doi:10.3892/ol.2019.11117

Cited by 3 publications

(5 citation statements)

References 35 publications

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“…Their binding relationship was ascertained by RNA pull‐down, while the binding site was validated by dual‐luciferase reporter gene assay. Moreover, miR‐23a‐3p has been reported to function as an oncogenic regulator of pancreatic cancer 12 . Existing literature has reported that FOXO3 is poorly expressed in pancreatic cancer, thus signifying its vital significance in tumorigenesis and cancer development, 36 which was consistent with our finding.…”

Section: Discussionsupporting

confidence: 91%

“…The results of dual‐luciferase reporter assay indicated that miR‐23a‐3p mimic inhibited the luciferase activity of LINC00472‐WT without altering that of LINC00472‐MUT (Figure 4D). Meanwhile, a high expression pattern of miR‐23a‐3p was reported in pancreatic cancer 12 . Therefore, we speculated that LINC00472 may regulate the development of pancreatic cancer through miR‐23a‐3p.…”

Section: Resultsmentioning

confidence: 92%

“…LincRNA 00472 (LINC00472) has demonstrated functionality as a competing endogenous RNA (ceRNA) to bind to several microRNAs (miRNAs) to suppress the progression of multiple types of cancers, including lung cancer 9 and colorectal cancer 10 . Additionally, miRNA has demonstrated to have vital significance in the development of human cancers by post‐transcriptional regulation of tumour suppressors or promoters, 11 and miR‐23a‐3p could exercise a tumour‐promoting effect on pancreatic cancer by targeting the transforming growth factor‐β receptor type II (TGFBR2) 12 . Moreover, forkhead box O3 (FOXO3) was a tumour suppressor targeted by miRNA in human pancreatic cancer progression, 13 while FOXO3a has been previously demonstrated to regulate BH3‐interacting domain death agonist (BID), which is a pro‐apoptotic protein belonging to the B‐cell lymphoma‐2 (Bcl‐2) protein family 14 .…”

Section: Introductionmentioning

confidence: 99%

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LINC00472 suppressed by ZEB1 regulates the miR‐23a‐3p/FOXO3/BID axis to inhibit the progression of pancreatic cancer

Wang

2021

J Cellular Molecular Medi

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The tumour‐suppressive role of LINC00472 has been extensively reported in various human cancers such as lung, colon and ovarian cancers, yet its function in pancreatic cancer remains unidentified. Here, the current research aimed to explore the role and regulatory axis mediated by LINC00472 in the progression of pancreatic cancer. RT‐qPCR was adopted to determine LINC00472 expression in the harvested pancreatic cancer tissues and adjacent normal tissues. Loss‐of‐function and gain‐of‐function experiments were performed to examine the effects of LINC00472 on proliferation and apoptosis in vitro and tumorigenesis in vivo. Immunoblotting was performed to detect the expression of several proliferation and apoptosis‐related proteins. Bioinformatic analysis, dual‐luciferase reporter assay and RNA pull‐down were conducted to profile the relationships between LINC00472 and miR‐23a‐3p, between miR‐23a‐3p and FOXO3 and between FOXO3 and BID. The LINC00472 expression was down‐regulated by ZEB1 in the pancreatic cancer cells and tissues. LINC00472 could competitively bind to miR‐23a‐3p to enhance the expression of FOXO3, which consequently could promote the BID expression, thereby suppressing proliferation and promoting the apoptosis of pancreatic cancer cells. Meanwhile, the inhibitory role of LINC00472 in tumorigenesis was validated in vivo, and the LINC00472‐mediated miR‐23a‐3p/FOXO3/BID axis was also demonstrated in the nude mouse tumour formation model. The study substantiated the antitumour activity of LINC00472 in pancreatic cancer and proposed a regulatory axis in which LINC00472 competitively binds to miR‐23a‐3p to enhance the FOXO3 expression and promote BID expression. Consequently, these findings provide theoretical basis for developing potential targets for the treatment of pancreatic cancer.

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Section: Discussionsupporting

confidence: 91%

Section: Resultsmentioning

confidence: 92%

Section: Introductionmentioning

confidence: 99%

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LINC00472 suppressed by ZEB1 regulates the miR‐23a‐3p/FOXO3/BID axis to inhibit the progression of pancreatic cancer

Wang

2021

J Cellular Molecular Medi

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“…Fan’s study showed that a higher FLR was significantly related to poor OS and DFS for ESCC ( 38 ). In ECC, Ji’s study showed that an increased NLR was related to poor prognosis for patients with DCC ( 39 ), and Lin’s study showed that a high LMR could predict poor prognosis in patients with PCC after R0 radical resection ( 11 ). However, these were not studies comparing the prognostic power of inflammatory indicators for ECC.…”

Section: Discussionmentioning

confidence: 99%

Preoperative peripheral blood inflammatory markers especially the fibrinogen-to-lymphocyte ratio and novel FLR-N score predict the prognosis of patients with early-stage resectable extrahepatic cholangiocarcinoma

Zhang

Lou

et al. 2022

Front. Oncol.

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BackgroundSystemic inflammation is important in the development of extrahepatic cholangiocarcinoma (ECC). The aim of this study was to compare the prognostic power of preoperative peripheral blood inflammatory markers and the novel FLR-N score in patients with resectable ECC.MethodsA total of 140 patients with resectable ECC and 140 healthy controls (HCs) were recruited for the study. The Mann−Whitney U test was used to evaluate the differences in inflammatory markers between groups. Kaplan−Meier and Cox regression analyses were used to evaluate the prognostic power of preoperative fibrinogen, albumin, prealbumin, bilirubin, neutrophils, lymphocytes, monocytes, platelets, fibrinogen-to-lymphocyte ratio (FLR), fibrinogen-to-albumin ratio (FAR), fibrinogen-to-prealbumin ratio (FPR), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), monocyte-to-lymphocyte ratio (MLR), FLR-neutrophil (FLR-N) score, and CA19-9 in patients with resectable ECC. Nomogram was developed based on the results of multivariate Cox analyses.ResultsPatients with resectable ECC had significantly higher levels of neutrophils, monocytes, fibrinogen, FLR, FAR, FPR, NLR, PLR, and MLR and lower levels of lymphocytes, albumin, and prealbumin than HCs (all P < 0.01). Albumin, prealbumin, and FPR had a good ability to distinguish between ECC patients with total bilirubin < 34 µmol/L and HCs (AUCs of 0.820, 0.827, and 0.836, respectively). Kaplan−Meier analysis showed that high neutrophil, fibrinogen, FLR, FAR, PLR, MLR, and FLR-N score values were associated with poor survival in patients with resectable ECC. Multivariate analyses indicated that neutrophils (P = 0.022), FLR (P = 0.040), FLR-N score (P < 0.0001), and positive lymph node metastasis (P = 0.016) were independent factors for overall survival (OS). Nomogram were developed to predict OS for patients with ECC.ConclusionThe prognostic roles of inflammatory markers in patients with resectable ECC were different. The preoperative neutrophil count, FLR and FLR-N score could serve as noninvasive markers for predicting the prognosis of resectable ECC.

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“…Therefore, we assumed that the regulation of RUNX2 on vascular injury repair might be achieved through regulating the expression of miR-23a. In addition, TGF-β receptor type II (TGFBR2), a predicted target gene of miR-23a, is important for cell proliferative and apoptotic potential (11). A recent study has demonstrated that TGFBR2 is implicated in the proliferation of smooth muscle cells (SMCs) after arterial injury, including the relevant repair process (12).…”

Section: Introductionmentioning

confidence: 99%

RUNX2 promotes vascular injury repair by activating miR-23a and inhibiting TGFBR2

Cai

Liu

et al. 2021

Ann Transl Med

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Background: Previous evidence has suggested that the transcription factor, runt-related transcription factor 2 (RUNX2), promotes the repair of vascular injury and activates the expression of microRNA-23a (miR-23a). TGF-β receptor type II (TGFBR2) has been found to mediate smooth muscle cells (SMCs) following arterial injury. However, the interactions among RUNX2, miR-23a and TGFBR2 in vascular injury have not been investigated thoroughly yet. Therefore, we aim to explore the mechanism of how RUNX2 triggers the expression of miR-23a and its effects on the repair of vascular injury.Methods: C57BL/6 mice were used to produce a model of arterial injury in vivo. Mouse arterial SMCs were isolated for in vitro cell injury induction by 100 nmol/L tumor necrosis factor-α (TNF-α). Gain-and lossof-function studies were conducted to assess cell viability and apoptosis by using cell counting kit (CCK)-8 assay and flow cytometry respectively. The levels of TNF-α, interleukin-6 (IL-6), and monocyte chemotactic protein-1 (MCP-1) were examined by enzyme-linked immunosorbent assay (ELISA). The interaction between RUNX2 and miR-23a was identified by chromatin immunoprecipitation (ChIP) and dual luciferase reporter assays, while the targeting relationship between miR-23a and TGFBR2 was analyzed by RNA immunoprecipitation (RIP) and dual luciferase reporter assays.Results: Both RUNX2 and miR-23a exhibited low levels of expressions, while TGFBR2 had a high level of expression in mice with induced arterial injury. RUNX2 was found to bind to the promoter of miR-23a and activate miR-23a, while miR-23a targeted TGFBR2. Ectopic RUNX2 expression inhibited inflammatory cell infiltration, and promoted collagen content by upregulating miR-23a and downregulating TGFBR2. Furthermore, the overexpression of RUNX2 increased viability and decreased apoptosis in vascular smooth muscle cells (VSMCs) by activating miR-23a. Conclusions:The overexpression of RUNX2 elevated the expression of miR-23, thus inhibiting TGFBR2 and promoting vascular injury repair.

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Insight into the effects of microRNA‑23a‑3p on pancreatic cancer and its underlying molecular mechanism

Cited by 3 publications

References 35 publications

LINC00472 suppressed by ZEB1 regulates the miR‐23a‐3p/FOXO3/BID axis to inhibit the progression of pancreatic cancer

LINC00472 suppressed by ZEB1 regulates the miR‐23a‐3p/FOXO3/BID axis to inhibit the progression of pancreatic cancer

Preoperative peripheral blood inflammatory markers especially the fibrinogen-to-lymphocyte ratio and novel FLR-N score predict the prognosis of patients with early-stage resectable extrahepatic cholangiocarcinoma

RUNX2 promotes vascular injury repair by activating miR-23a and inhibiting TGFBR2

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