A cancer-testis non-coding RNA LIN28B-AS1 activates driver gene LIN28B by interacting with IGF2BP1 in lung adenocarcinoma

Wang, Cheng; Gu, Yayun; Zhang, Erbao; Zhang, Kai; Qin, Na; Dai, Juncheng; Zhu, Meng; Liu, Jia; Xie, Kaipeng; Jiang, Yue; Guo, Xuejiang; Liu, Mingxi; Jin, Guangfu; Ma, Hongxia; Jiang, Tao; Yin, Rong; Xia, Yankai; Liu, Li; Wang, Shouyu; Shen, Bin; Huo, Ran; Xu, Lin; Sha, Jiahao; Qu, Bin; Shen, Hongbing

doi:10.1038/s41388-018-0548-x

Cited by 62 publications

(57 citation statements)

References 45 publications

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“…Cancer-testis (CT) genes, which express only in germ cells and cancer cells, may be the basis of the above theory and participated in the process of carcinogenesis and cancer metastasis. Our previous work systematically identified CT genes in cancer patients and revealed that CT genes could be a new source of epi-driver candidates of cancers (2,3), which were also supported by the other recent studies (4). Several CT genes, such as MAGEA3, FATE1, and LIN28B have been proved to contribute to the infinite proliferation of cancer cells (3)(4)(5).…”

Section: Introductionsupporting

confidence: 68%

Meiosis related cancer-testis genes correlate with tumor aneuploidy and immune infiltration in 21 cancer types

Wang

Chang

et al. 2019

Preprint

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The meiosis stage of spermatogenesis and the aneuploidy generation in tumorigenesis are highly linked. Cancer-testis genes (CT genes) were specifically expressed in testis and cancers and may serve as the molecular basis of the shared features between spermatogenesis and tumorigenesis. In the present study, we integrated multi-omics data from bulk samples and cell lines, and single cell RNA-Seq data from testis and two tumors to systematically investigate the association between CT genes and aneuploidy. After ranking genes according to their association with aneuploidy level, we found that CT genes, especially CT genes specifically expressed in meiosis, showed a consistently positive correlation with aneuploidy and homologous recombination deficiency (HRD) level. Similar results were also found in the CT non-coding genes. Then, we constructed a regulatory network based on the single cell RNA-seq data and revealed that the gain of accelerator transcriptional factors (TFs) E2F7 and E2F8 and the loss of the stabilizer TFs RFX2 and NFYA aberrantly activated CT genes in the cancers and were associated with the increase of HRD level. Finally, we found that the association between CT genes and cytotoxic infiltrating lymphocytes can be influenced by the HRD level. In sum, our results revealed the evidence of pseudomeiotic functions of CT genes in the aneuploidy generation process in the cancer cells. The results may help illuminate the origin of aneuploidy in cancers and guide future immunotherapy targeting CT antigens.

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Section: Introductionsupporting

confidence: 68%

Meiosis related cancer-testis genes correlate with tumor aneuploidy and immune infiltration in 21 cancer types

Wang

Chang

et al. 2019

Preprint

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“…[29][30][31][32][33] Accordingly, lncRNAs are increasing being identified as crucial regulators in human tumors. Among these, antisense lncRNA is emerging as a vital participant with respect to affecting various cancerous developments, [34][35][36][37][38] In the present study, five candidates (DICER1-AS1, FAM83H-AS1, GPC3-AS1, DLX6-AS1 and SOX21-AS1) were subjected to qRT-PCR. [42][43][44][45][46] GPC3-AS1 was found to be significantly up-regulated in all four CC cell lines compared to the normal cell CRL-2614.…”

Section: Discussionmentioning

confidence: 99%

“…Accordingly, lncRNAs are increasing being identified as crucial regulators in human tumors. Among these, antisense lncRNA is emerging as a vital participant with respect to affecting various cancerous developments, including CC. Rui et al .…”

Section: Discussionmentioning

confidence: 99%

ELK1‐activated GPC3‐AS1/GPC3 axis promotes the proliferation and migration of cervical cancer cells

Zhu

2019

The Journal of Gene Medicine

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Background Long non‐coding RNA (lncRNA) is reported to be involved in multiple biological processes in numerous human tumors. Furthermore, an increasing number of studies have confirmed the involvement of lncRNA in the initiation and development of human cancers, including cervical cancer (CC). Methods The present study explored the potential role of lncRNA glypican 3 antisense transcript 1 (GPC3‐AS1) with respect to regulating CC cell proliferation and migration. Results A quantitative reverse transcriptase‐polymerase chain reaction confirmed that GPC3‐AS1 was up‐regulated in CC cells compared to normal CRL‐2614 cells. Loss‐of‐function assays demonstrated the negative effect of GPC3‐AS1 depletion on CC cell proliferation and migration. GPC3‐AS1 positively regulated its nearby gene glypican 3 (GPC3). Significant up‐regulation of GPC3 was also observed in CC cells, consistently with GPC3‐AS1. In addition, GPC3‐AS1 and GPC3 synergistically promoted the proliferative and migratory abilities of CC cells. Mechanistic investigation showed that ELK1 acted as the transcription activator of GPC3‐AS1 and GPC3, thus contributing to their up‐regulation in CC cells. Rescue assays indicated that the ELK1‐induced GPC3‐AS1/GPC3 axis promoted cell proliferation and migration in CC. Conclusions The results of the present study have revealed a novel molecular pathway that can regulate CC cell proliferation and migration, thus providing a new basis for investigating the molecular mechanism associated with CC progression.

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“…For example, Tony et al showed that the noncoding RNA MALAT1 was a critical regulator in lung cancer metastasis (Tony et al, 2013). Wang et al, (2018) found that LIN28B…”

Section: Discussionmentioning

confidence: 99%

Pseudogene CHIAP2 inhibits proliferation and invasion of lung adenocarcinoma cells by means of the WNT pathway

Shang

Wang

Chen

et al. 2019

Journal Cellular Physiology

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Recently, pseudogenes have emerged as critical regulators in the onset of human neoplasia. Here, we present a comprehensive analysis of pseudogene alterations at transcriptional levels in lung adenocarcinoma (LUAD) from The Cancer Genome Atlas. By combinations of differential expression analysis, survival analysis, and univariate and multivariable Cox proportional hazards regression models, we identified four dysregulated pseudogenes, whose expression level was closely related to LUAD patients' prognosis and the four pseudogene signature could act as an independent prognostic indicator for LUAD patients. We further characterized CHIAP2, one of those four pseudogenes, whose expression level was the most closely linked to LUAD patients' prognosis. Consistent with our analysis, the expression of CHIAP2 was abnormally downregulated in LUAD tissues compared with that in normal tissues in our 50 pairs of clinical samples. Functional assays demonstrated that upregulation of CHIAP2 significantly impaired cell proliferation and invasion. After performing RNA sequencing (RNA‐seq) and small RNA‐seq between CHIAP2 overexpression and negative control LUAD cell lines, we identified differentially expressed messenger RNAs and microRNAs (miRNAs), among which six miRNAs were downregulated. Target genes of six downregulated miRNAs were predicted with online miRNA target prediction tools and significant pathways including the WNT signal pathway were identified with Gene Set Enrichment Analysis. By combining predictor genes of six downregulated miRNAs and dysregulated genes of the WNT pathway, we inferred that overexpression of CHAP2 may inhibit LUAD cell proliferation and invasion via modulation of NFATC2 or GSK3B (WNT signal pathway) targeted by miR‐3614‐5p or miR‐873‐3p.

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A cancer-testis non-coding RNA LIN28B-AS1 activates driver gene LIN28B by interacting with IGF2BP1 in lung adenocarcinoma

Cited by 62 publications

References 45 publications

Meiosis related cancer-testis genes correlate with tumor aneuploidy and immune infiltration in 21 cancer types

Meiosis related cancer-testis genes correlate with tumor aneuploidy and immune infiltration in 21 cancer types

ELK1‐activated GPC3‐AS1/GPC3 axis promotes the proliferation and migration of cervical cancer cells

Pseudogene CHIAP2 inhibits proliferation and invasion of lung adenocarcinoma cells by means of the WNT pathway

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