Targeting PELP1 Attenuates Angiogenesis and Enhances Chemotherapy Efficiency in Colorectal Cancer

Zhu, Jianlin; Wang, Lu; Li, Fan; Pan, Jinghua; Yao, Ziting; Lin, Yusheng; Yang, Yabing; Xiong, Xi; Li, Kai; Yang, Yi; Zhang, Yiran; Chu, Xiangxiang; Pan, Yunlong; Zhang, Hao

doi:10.3390/cancers14020383

Cited by 4 publications

(5 citation statements)

References 52 publications

(57 reference statements)

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“…PELP1 directly bound to the promoter sequences of miR-200a and recruited HDAC2, which decreased the expression of miR-200a in breast cancer cells [ 129 ]. The downregulation of PELP1 enhanced the efficacy of chemotherapy by suppressing signal transducer and activator of transcription 3 (STAT3)/vascular endothelial growth factor (VEGF) signaling in colorectal cancer cells [ 130 ]. The downregulation of PELP1 enhanced the sensitivity of breast cancer cells to genotoxic agents by suppressing the cell cycle and enhancing apoptosis [ 131 ].…”

Section: Role Of the Mir-200 Family In Anti-cancer Drug Resistancementioning

confidence: 99%

Potential of the miR-200 Family as a Target for Developing Anti-Cancer Therapeutics

Shim

Jeoung

2022

IJMS

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MicroRNAs (miRNAs) are small non-coding RNAs (18–24 nucleotides) that play significant roles in cell proliferation, development, invasion, cancer development, cancer progression, and anti-cancer drug resistance. miRNAs target multiple genes and play diverse roles. miRNAs can bind to the 3′UTR of target genes and inhibit translation or promote the degradation of target genes. miR-200 family miRNAs mostly act as tumor suppressors and are commonly decreased in cancer. The miR-200 family has been reported as a valuable diagnostic and prognostic marker. This review discusses the clinical value of the miR-200 family, focusing on the role of the miR-200 family in the development of cancer and anti-cancer drug resistance. This review also provides an overview of the factors that regulate the expression of the miR-200 family, targets of miR-200 family miRNAs, and the mechanism of anti-cancer drug resistance regulated by the miR-200 family.

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Section: Role Of the Mir-200 Family In Anti-cancer Drug Resistancementioning

confidence: 99%

Potential of the miR-200 Family as a Target for Developing Anti-Cancer Therapeutics

Shim

Jeoung

2022

IJMS

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“…26 This also suggests that VEGFA may play an important role in tumor proliferation, invasion and metastasis as a growth factor involved in angiogenesis; therefore, inhibiting VEGFA expression may inhibit angiogenesis and tumor growth. [27][28][29] Importantly, several studies on UCs have also suggested that VEGF and FGF are the main angiogenic factors in bladder cancer cells and that VEGF levels in the urine and blood are associated with the stage, metastasis, recurrence rate and prognosis of cancer. [30][31][32][33] However, no studies have reported the direct regulation of VEGFA expression by miRNAs in UTUC to date.…”

Section: Introductionmentioning

confidence: 99%

“…Recently, it has been shown that VEGFA expression correlates with the prognosis of malignant tumors, including colorectal cancer, 23 breast cancer, 24 endometrial cancer 25 and gastric cancer 26 . This also suggests that VEGFA may play an important role in tumor proliferation, invasion and metastasis as a growth factor involved in angiogenesis; therefore, inhibiting VEGFA expression may inhibit angiogenesis and tumor growth 27–29 . Importantly, several studies on UCs have also suggested that VEGF and FGF are the main angiogenic factors in bladder cancer cells and that VEGF levels in the urine and blood are associated with the stage, metastasis, recurrence rate and prognosis of cancer 30–33 .…”

Section: Introductionmentioning

confidence: 99%

MicroRNA‐299‐3p inhibits cell proliferation, motility, invasion and angiogenesis via VEGFA in upper tract urothelial carcinoma

Wang,

Lee,

Jhan

et al. 2023

The Journal of Gene Medicine

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BackgroundUpper tract urothelial carcinoma (UTUC) is a rare tumor with extraordinarily different features between Eastern and Western countries. Vascular endothelial growth factor‐A (VEGFA) was originally identified as a secreted signaling protein and regulator of vascular development and cancer progression. In this study, we aimed to elucidate the molecular mechanisms underlying the regulation of VEGFA by microRNA in UTUC.MethodsVEGFA expression was evaluated by immunohistochemistry in 140 human UTUC tissue samples. Next, we assessed the regulatory relationship between VEGFA and miR‐299‐3p by real‐time PCR, western blotting, ELISA and dual‐luciferase reporter assays using two UTUC cell lines. The role of miR‐299‐3p/VEGFA in cell proliferation, motility, invasion, and tube formation was analyzed in vitro.ResultsHigh VEGFA expression was significantly associated with tumor stage, grade, distant metastasis and cancer‐related death and correlated with poor progression‐free and cancer‐specific survival. VEGFA knockdown repressed proliferation, migration, invasion and angiogenesis in UTUC cell lines. miR‐299‐3p significantly reduced VEGFA protein expression and miR‐299‐3p overexpression inhibited VEGFA mRNA and protein expression by directly targeting its 3′‐UTR. Functional studies indicated that VEGFA overexpression reversed the miR‐299‐3p‐mediated suppression of tumor cell proliferation, migration, invasion and angiogenesis. In addition, miR‐299‐3p/VEGFA suppressed cellular functions in UTUC by modulating the expression of P18 and cyclin E2.ConclusionsOur findings suggest that miR‐299‐3p possibly suppresses UTUC cell proliferation, motility, invasion and angiogenesis via VEGFA. VEGFA may act as a prognostic predictor, and both VEGFA and miR‐299‐3p could be potential therapeutic targets for UTUC.

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“…Recent studies have found that angiogenesis in the tumor microenvironment is critical to the recurrence and distant organ metastasis of CRC because blood is required to provide essential oxygen and nutrients during these processes [ 3 – 5 ]. Currently, anti-angiogenesis therapy has been one of the most commonly used methods for the treatment of tumor recurrence and drug-resistant distant organ metastasis.…”

Section: Introductionmentioning

confidence: 99%

METTL3 dual regulation of the stability of LINC00662 and VEGFA RNAs promotes colorectal cancer angiogenesis

et al. 2022

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Purpose The angiogenesis is among the primary factors that affect tumor recurrence and distant organ metastasis in colorectal cancer (CRC). N 6-methyladenosine (m6A) modification is one of the most common chemical modifications in eukaryotic mRNA, especially at the post-transcriptional level. Methyltransferase-like 3 (METTL3) promoting angiogenesis in a variety of tumors has been reported. However, the mechanism of how METTL3 dual-regulates the stability of long non-coding RNAs (lncRNAs) and vascular-related factor RNAs to affect angiogenesis in CRC is unclear. Methods 64 paired CRC and adjacent normal tissues were collected. In vitro, quantitative real-time polymerase chain reaction (qRT-PCR), immunohistochemistry (IHC), actinomycin assay, methylated RNA immunoprecipitation (MeRIP) experiment,3-(4,5)-dimethylthiahiazo(-z-y1)-3,5-di-phenytetrazoliumromide (MTT) and colony formation assay were performed. The functions were also studied in zebrafish model animals in vivo. Results We found that the vascular endothelial growth factor A(VEGFA), METTL3 and LINC00662 RNAs were highly expressed in CRC, and that METTL3 was significantly positively correlated with LINC00662 and VEGFA. The protein expression levels of CD31, CD34, VEGFA, m6A and METTL3 were all significantly increased in the CRC tissues. The angiogenesis experiments both in vivo and in vitro found that METTL3 and LINC00662 promoted angiogenesis in CRC. The actinomycin assay indicated that METTL3 maintained the stability of LINC00662 and VEGFA RNAs. In addition, the MeRIP experiment confirmed that the LINC00662 and VEGFA RNAs had METTL3-enriched sites. Conclusion These findings suggest that METTL3 and LINC00662 may both serve as diagnostic and prognostic predictive biomarkers for CRC and potential targets for anti-vascular therapy. Supplementary Information The online version contains supplementary material available at 10.1007/s12672-022-00557-3.

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Targeting PELP1 Attenuates Angiogenesis and Enhances Chemotherapy Efficiency in Colorectal Cancer

Cited by 4 publications

References 52 publications

Potential of the miR-200 Family as a Target for Developing Anti-Cancer Therapeutics

Potential of the miR-200 Family as a Target for Developing Anti-Cancer Therapeutics

MicroRNA‐299‐3p inhibits cell proliferation, motility, invasion and angiogenesis via VEGFA in upper tract urothelial carcinoma

METTL3 dual regulation of the stability of LINC00662 and VEGFA RNAs promotes colorectal cancer angiogenesis

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