Long noncoding RNAs: functions and mechanisms in colon cancer

Chen, Sian; Shen, Xian

doi:10.1186/s12943-020-01287-2

Cited by 216 publications

(172 citation statements)

References 89 publications

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“…Cancer cells aquire drug resistance through different mechanisms ( Chen and Shen, 2020 ; da Costa and Baiocchi, 2020 ; Qin et al, 2020 ; Zhu et al, 2020 ; Pastushenko et al, 2021 ), including enhancement of oxygen free radical scavenging, promotion of DNA damage repair, or inhibition of apoptotic signaling pathway activation ( Lü et al, 2008 ; Bakkenist et al, 2018 ; Phi et al, 2018 ). In vitro studies suggest a role for SOX9 in regulating cell differentiation in the intestinal epithelium ( Mori-Akiyama et al, 2007 ; Aguilar-Medina et al, 2019 ).…”

Section: Discussionmentioning

confidence: 99%

The SOX9-MMS22L Axis Promotes Oxaliplatin Resistance in Colorectal Cancer

Liu

Luo

et al. 2021

Front. Mol. Biosci.

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BackgroundColorectal cancer (CRC) is estimated to be one of the most common cancers and the leading cause of cancer-related death worldwide. SOX9 is commonly overexpressed in CRC and participates in drug resistance. In addition, DNA damage repair confers resistance to anticancer drugs. However, the correlation between DNA damage repair and high SOX9 expression is still unclear. In this study, we aimed to investigate the function and the specific underlying mechanism of the SOX9-dependent DNA damage repair pathway in CRC.MethodsThe expression levels of SOX9 and MMS22L in CRC were examined by immunohistochemistry (IHC) and TCGA analysis. RNA sequencing was conducted in RKO SOX9-deficient cells and RKO shControl cells. Mechanistic studies were performed in CRC cells by modulating SOX9 and MMS22L expression, and we evaluated drug sensitivity and DNA damage repair signaling events. In addition, we investigated the effect of oxaliplatin in tumors with SOX9 overexpression and low expression of MMS22L in vivo.ResultsOur study showed that SOX9 has a higher expression level in CRC tissues than in normal tissues and predicts poor prognosis in CRC patients. Overexpression and knockdown of SOX9 were associated with the efficacy of oxaliplatin. In addition, SOX9 activity was enriched in the DNA damage repair pathway via regulation of MMS22L expression and participation in DNA double-strand break repair. SOX9 was upregulated and formed a complex with MMS22L, which promoted the nuclear translocation of MMS22L upon oxaliplatin treatment. Moreover, the xenograft assay results showed that oxaliplatin abrogated tumor growth from cells with MMS22L downregulation in mice.ConclusionsIn CRC, activation of the SOX9-MMS22L-dependent DNA damage pathway is a core pathway regulating oxaliplatin sensitivity. Targeting this pathway in oxaliplatin-resistant CRC cells is a promising therapeutic option.

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Section: Discussionmentioning

confidence: 99%

The SOX9-MMS22L Axis Promotes Oxaliplatin Resistance in Colorectal Cancer

Liu

Luo

et al. 2021

Front. Mol. Biosci.

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“…At present, the clinical relationship between lncRNAs and human cancer is a research hotspot in tumour molecular biology given their importance in tumorigenesis and tumour development [23][24][25]. Therefore, lncRNAs may be attractive therapeutic targets for tumour intervention.…”

Section: Discussionmentioning

confidence: 99%

Silencing of Long Noncoding RNA LINC01132 Alleviates the Oncogenicity of Epithelial Ovarian Cancer by Regulating the microRNA-431-5p/SOX9 Axis

Zhu

Xiao

Chen

2021

Preprint

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Background: To date, long intergenic nonprotein coding RNA 1132 (LINC01132) expression in epithelial ovarian cancer (EOC) and the underlying mechanisms have not been explored. In this study, we measured LINC01132 expression in EOC and assessed the effects of LINC01132 on the malignant behaviours of EOC cells in vitro and in vivo. Additionally, mechanistic studies were performed to elucidate the molecular events that occurred downstream of LINC01132 in EOC cells. Methods: Reverse-transcription quantitative PCR (RT-qPCR) was utilized to verify LINC01132 expression in EOC. The effects of LINC01132 on the malignant behaviours of EOC cells were determined using a Cell Counting Kit-8 assay, flow cytometry analysis, cell migration and invasion assays and a tumour xenograft model. The targeting interaction among LINC01132, microRNA-431-5p (miR-431-5p) and SRY-Box 9 (SOX9) was verified by RNA immunoprecipitation and luciferase reporter assays. Results: LINC01132 was overexpressed in EOC and was obviously associated with poor patient prognosis. Functionally, cell experiments revealed that LINC01132 depletion could inhibit EOC cell proliferation, migration and invasion and promote cell apoptosis in vitro. Additionally, loss of LINC01132 attenuated tumour growth in vivo. Mechanistically, LINC01132 acted as a competing endogenous RNA by sequestering miR-431-5p and thereby increasing SOX9 expression in EOC cells, forming a LINC01132/miR-431-5p/SOX9 axis. In rescue experiments, miR-431-5p inhibition or SOX9 re-expression eliminated the inhibitory effects of LINC01132 silencing on the pathological behaviours of EOC cells. Conclusions: Generally, LINC01132 exhibited oncogenic activities in EOC cells in vitro and in vivo by regulating the outcome of the miR-431-5p/SOX9 axis, providing an effective target for EOC diagnosis, therapy and prognosis evaluation.

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“…In recent years, Wnt-targeting therapeutics in other cancer types are in different phases of pre-clinical or early clinical trials, while those for osteosarcoma are still scarcely observed [ 6 , 41 ]. Recently, lncRNAs are gaining researchers’ attention as an alternative strategy for cancer treatment [ 22 , 183 , 184 ]. The increasing insights into the crosstalk between lncRNAs and Wnt in osteosarcoma may lead to the development of promising pharmacological candidates (Shown in Fig.…”

Section: Conclusion and Future Perspectivesmentioning

confidence: 99%

“…LncRNAs could participate in diverse biological processes, including cell survival, apoptosis, differentiation, DNA damage repair, and inflammation [ 21 ]. Mechanistically, the most commonly reported feature of lncRNAs is to act as a competing endogenous RNA (ceRNA) to regulate miRNA expression and thus to target downstream genes [ 22 ]. Besides, lncRNAs could also interact with macromolecules such as DNA, RNA and proteins to modulate expression of target genes at transcriptional, posttranscriptional and translational level, providing for multiple layers of control, as shown in Fig.…”

Section: Introductionmentioning

confidence: 99%

Functional interplay between long non-coding RNAs and the Wnt signaling cascade in osteosarcoma

Lin

Liu

et al. 2021

Cancer Cell Int

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Osteosarcoma is a common and highly malignant bone tumor among children, adolescents and young adults. However, the underlying molecular mechanisms remain largely unexplored. LncRNAs are transcripts with no or limited protein-coding capacity in human genomes, and have been demonstrated to play crucial functions in initiation, progression, therapeutic resistance, recurrence and metastasis of tumor. Considerable studies revealed a dysregulated lncRNA expression pattern in osteosarcoma, which may act as oncogenes or suppressors to regulate osteosarcoma progression. Wnt signaling pathway is an important cascade in tumorigenesis by modulation of pleiotropic biological functions including cell proliferation, apoptosis, differentiation, stemness, genetic stability and chemoresistance. Hyperactivation or deficiency of key effectors in Wnt cascade is a common event in many osteosarcoma patients. Recently, increasing evidences have suggested that lncRNAs could interplay with component of Wnt pathway, and thereby contribute to osteosarcoma onset, progression and dissemination. In this review, we briefly summarize Wnt signaling-related lncRNAs in osteosarcoma progression, aiming to gain insights into their underlying crosstalk as well as clinical application in osteosarcoma therapeutic modalities.

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Long noncoding RNAs: functions and mechanisms in colon cancer

Cited by 216 publications

References 89 publications

The SOX9-MMS22L Axis Promotes Oxaliplatin Resistance in Colorectal Cancer

The SOX9-MMS22L Axis Promotes Oxaliplatin Resistance in Colorectal Cancer

Silencing of Long Noncoding RNA LINC01132 Alleviates the Oncogenicity of Epithelial Ovarian Cancer by Regulating the microRNA-431-5p/SOX9 Axis

Functional interplay between long non-coding RNAs and the Wnt signaling cascade in osteosarcoma

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