2025 Hyper Recent •CC0 1.0 Universal

This work is dedicated to the public domain. No rights reserved.

Access Preprint From Server
April 21st, 2025
Version: 4
NIH
cancer biology
biorxiv

The lnc-FANCI-2 intrinsically restricts RAS signaling in HPV16-infected cervical cancer

Liu, H.Open in Google Scholar•Yu, L.Open in Google Scholar•Majerciak, V.Open in Google Scholar•Meyer, T.Open in Google Scholar•Yi, M.Open in Google Scholar•Johnson, P. F.Open in Google Scholar•Cam, M.Open in Google Scholar•Lowy, D. R.Open in Google Scholar•Zheng, Z.-M.Open in Google Scholar

We recently discovered the expression of a long noncoding RNA, lnc-FANCI-2, coinciding with cervical lesion progression from CIN1, CIN2-3 to cervical cancer. Viral E7 of high-risk HPVs and host transcription factor YY1 are two major factors promoting lnc-FANCI-2 expression. To explore possible roles of lnc-FANCI-2 in HPV-induced cervical carcinogenesis, we ablated the expression of lnc-FANCI-2 in the HPV16-positive cervical cancer cell line, CaSki. Knock-out (KO) single cell clones expressed HPV16 oncogenes normally but displayed altered cell morphology and proliferation when compared with the parental cells. Proteomic profiling of cytosolic and secreted proteins from the parental and KO cells showed that lnc-FANCI-2 regulates expression of a subset of cell soluble receptors responsible for cell signaling, epithelial mesenchymal transition, and IFN responses. RNA-seq analyses revealed that, relative to the parental cells, lnc-FANCI-2 KO cells exhibited significantly increased RAS signaling but decreased IFN pathways. In the KO cells, phosphorylated Akt and Erk1/2, two important RAS pathway effectors, were increased more than 3-fold, accompanied by increase of IGFBP3, MCAM, VIM, and CCND2 (cyclin D2) and decrease of RAC3 expression. High levels of lnc-FANCI-2 and lower levels of MCAM in cervical cancer patients are associated with improved survival. We found that lnc-FANCI-2 interacts specifically with 32 host proteins, including H13, HNRH1, K1H1, MAP4K4, and RNPS1, and knockdown of MAP4K4 in CaSki cells led to an increase of phosphorylation of Erk1/2 and somewhat Akt. In summary, a key function of lnc-FANCI-2 is to intrinsically regulate RAS signaling to impact cervical lesion progression and affect cervical cancer prognosis.

Similar Papers

biorxiv
Mon Apr 21 2025
The novel RNA polymerase I transcription inhibitor PMR-116 exploits a critical therapeutic vulnerability in a broad-spectrum of high MYC malignancies.
Ribosome biogenesis (RiBi) is a key determinant of cell growth and proliferation and is highly elevated in cancer due to the activation by oncogenes such as MYC. First-generation RiBi inhibitor CX-5461, while demonstrating clinical potential for cancer treatment, also induces DNA damage through off-target inhibition of TOP2 and potentially other mechanisms, bringing into question RiBi as a target ...
Ferreira, R.
•
Hannan, K. M.
•
Panov, K.
•
Udumanne, T.
...•
Hein, N.
biorxiv
Mon Apr 21 2025
Human Papilloma Virus does not fully inactivate p53 cellular activity in HNSCC
Head and neck squamous cell carcinoma (HNSCC) is a major global health challenge. Inactivation of the tumor suppressor p53 is the most frequent molecular event in this malignancy. p53 inactivation occurs either through TP53 mutations in human papilloma virus (HPV)-negative cases or via HPV-mediated p53 degradation in HPV-positive (HPV+) cases, where most tumors retain a wild-type (WT) TP53 allele....
Gencel-Augusto, J.
•
Li, H.
•
Woerner, L. C.
•
Borah, A. A.
...•
Grandis, J. R.
biorxiv
Mon Apr 21 2025
Phosphoproteomics Uncovers Tumor Heterogeneity and Therapeutic Opportunities in Early-Stage Hepatocellular Carcinoma
Background and Aims: Hepatocellular carcinoma (HCC) is a highly heterogeneous cancer, with mechanisms of initiation, progression, and recurrence not fully clarified. While prior large-scale phosphoproteomic studies in HCC have mapped phosphorylation dynamics and identified subgroups consistent with proteomic subgroups, the role of phosphorylation in early-stage HCC heterogeneity and therapeutic vu...
Ren, L.
•
Jiang, J.
•
Lin, W.
•
Qi, L.
...•
Jiang, Y.
biorxiv
Mon Apr 21 2025
NOX4 prevents the recruitment of PAX8 and NKX2.1 to chromatin in BRAF-mutated thyroid cancer cells.
Radioiodine (RAI) therapy, used for treating thyroid cancers, hinges on the expression of the Sodium Iodide Symporter (NIS). The majority of differentiated thyroid cancers (DTCs) are papillary, with a BRAFV600E mutation. This mutation correlates with an absence of RAI uptake, due to low NIS expression and a low differentiation score. NADPH oxidase 4 (NOX4)-derived ROS contribute to NIS repression ...
Radom, M.
•
Buffet, C.
•
Cazarin, J.
•
Harinquet, M.
...•
DUPUY, C.
biorxiv
Mon Apr 21 2025
A small molecule inhibitor of RNA-binding protein IGF2BP3 shows anti-leukemic activity
The RNA-binding protein IGF2BP3 is an oncofetal protein overexpressed in B-acute lymphoblastic leukemia and is critical for leukemogenesis in experimental models. With cancer-specific expression, functional dispensability for normal development, and an unleveraged pro-oncogenic function in mRNA homeostasis, IGF2BP3 represents an excellent target. With no small molecule inhibitors of IGF2BP3 in cli...
Jaiswal, A. K.
•
Scherer, G. M.
•
Thaxton, M. L.
•
Sorrentino, J. P.
...•
Rao, D. S.
biorxiv
Mon Apr 21 2025
Single-Cell Pharmacogenomic Landscapes of Epigenetic Therapy in Gastric Cancer
Gene expression signatures (\"molecular phenotypes\") are extensively utilized in cancer research. Using direct capture Perturb-seq (dcPerturb-seq), we surveyed how molecular phenotypes in gastric cancer (GC) are shaped by cell-intrinsic genetic alterations interacting with cell-extrinsic therapeutic exposures. Interrogating >200 GC-related genes against 4 distinct epigenetic drug classes across m...
Xu, C.
•
Ma, H.
•
Sheng, T.
•
Lee, M. H.
...•
Tan, P.
biorxiv
Fri Apr 18 2025
New Δ246p53 isoform responds to DNA damage to enhance p53 functions in senescence and tumour suppression
p53 is with little doubt one of the most powerful genes in our genome, as it makes growth vs arrest, repair vs replacement, metabolism vs anabolism, life vs death decisions in the cell. An alteration or malfunction in p53 may lead to cancer or premature ageing. So, it is not surprising that p53 is also one of the most complex and tightly regulated genes. p53 alone encodes for at least 10 RNA varia...
Parkar, S. N.
•
Ramalho, A. C.
•
Lopez-Iniesta, M. J.
•
Kimura, K.
...•
Candeias, M. M.
biorxiv
Fri Apr 18 2025
Transcriptional regulators FOXD1 and RBFOX2 contribute to metastatic capacity in BAP1mut uveal melanoma
Uveal melanoma is the most prevalent primary intraocular cancer, with a significant metastatic risk. This risk is dependent on the genetic drivers. Secondary mutations in EIF1AX, SF3B1 and BAP1 correlate with clinical outcomes and are recognized for their distinct transcriptomic and epigenetic profiles. Previously, we identified 480 genes involved in the development of ocular melanocytes. Top rank...
Brosens, E.
•
Nguyen, J.
•
Konemann, N.
•
van den Bosch, T.
...•
van den Bosch, Q.
biorxiv
Fri Apr 18 2025
SKIDA1 transiently sustains MLL::ENL-Expressing hematopoietic progenitors during neonatal stages and promotes B-lineage priming
Infant leukemias arise as B-cell acute lymphocytic (B-ALL) or acute myeloid leukemia (AML). The majority are driven by chromosomal rearrangements of the MLL/ KMT2A gene (MLLr) and arise in utero, implying a fetal cell of origin. Fetal and neonatal hematopoietic progenitors have unique transcriptomes and epigenomes, raising the question of whether MLL fusion proteins activate distinct target gene p...
Mendoza-Castrejon, J.
•
Yang, W.
•
Denby, E.
•
Muthukumar, R.
...•
Magee, J. A.