The hnRNPK/A1/R/U Complex Regulates Gene Transcription and Translation and is a Favorable Prognostic Biomarker for Human Colorectal Adenocarcinoma

Abstract

Heterogeneous nuclear ribonucleoproteins (hnRNPs) are emerging as a crucially important protein family in tumors. However, it is unclear which family members are essential for cancer progression, and their diverse expression patterns and prognostic values are rarely reported. In this work, we found that the expression levels of hnRNPs were all upregulated in colon adenocarcinoma (COAD) and rectal adenocarcinoma (READ) tissues. Immunohistochemical staining revealed that hnRNPA1, hnRNPA2B1, hnRNPC, hnRNPK, hnRNPR, and hnRNPU are overexpressed in colorectal adenocarcinoma. Additionally, the promoter methylation levels of hnRNPs were significantly elevated or decreased, and multiple genetic alterations of hnRNPs were found in colorectal adenocarcinoma patients. Correlation analysis showed that the expression levels of hnRNPs were positively correlated with each other. Furthermore, we demonstrated that high expressions of hnRNPA1, hnRNPK, hnRNPR, and hnRNPU were associated with better overall survival rates for colorectal adenocarcinoma patients. The co-expression network and functional prediction analysis indicated that hnRNPK/A1/R/U was involved in cellular gene transcription and translation. Moreover, hnRNPK/A1/R/U complex was identified and confirmed by mass spectrometry and co-immunoprecipitation. RNA sequencing analysis revealed that the transcription factor hnRNPK regulated transcription and translation of related genes. Finally, through establishment of stable cell lines in vitro, we verified that hnRNPK was a favorable factor in human colorectal adenocarcinoma which promoted immune cell infiltration and inhibited tumor growth. Our findings illustrate that the hnRNPK/A1/R/U complex is a favorable prognostic biomarker for human colorectal adenocarcinoma. Targeting hnRNPK during transcription and translation could be a promising therapeutic strategy for colorectal adenocarcinoma treatment.

Decoding Complexity in Biomolecular Recognition of Dna I-Motifs

“…It has been proposed that these proteins belong to distinct subgroups within the hnRNP family, where hnRNP A1 is involved in core complex formation and hnRNP K plays roles in RNA regulation [42] . Recently, it was shown that hnRNP A1, R, U, and K form a complex in colon and rectal adenocarcinoma cells, in which hnRNP K regulated translation of relevant genes [43] . When cross-referencing the published co-expression network of the hnRNP A1/R/U/K complex with the array hnRNP K data, we see that several genes identified are hits.…”

Pan‐cancer analysis of the oncogenic role of HNRNPR in human tumors

“…The researchers found that high expression of HNRNPR predicted increased OS rates in COAD based on the HPA webtool, although they did not explore the potential mechanism of HNRNPR in COAD or the effect of HNRNPR on cancer cells (Y. Li et al, 2022). Moreover, there is one report highlighting the role of the hnRNP family in pan-cancer.…”

“…Recently, it has been reported that HNRNPR overexpression correlated with 18F‐FDG uptake in ESCA, and HNRNPR expression could predict poor survival in ESCA patients (X. Y. Liu et al, 2022). The researchers found that high expression of HNRNPR predicted increased OS rates in COAD based on the HPA webtool, although they did not explore the potential mechanism of HNRNPR in COAD or the effect of HNRNPR on cancer cells (Y. Li et al, 2022). Moreover, there is one report highlighting the role of the hnRNP family in pan‐cancer.…”

Inhibition of the macrophage demethylase LSD1 reversesLeishmania amazonensis-induced transcriptomic changes and causes a decrease in parasite load

“…Likewise, other infection-specific LSD1 interactions may favor parasite survival, such as the splicing factor proline- and glutamine-rich (SFPQ), the ATP-dependent RNA helicase A (DHX9), and Matrin 3 (MATR3), and the non-POU domain-containing octamer-binding protein (NONO). These molecules are respectively involved in i) viral RNA amplification (Labeau et al, 2022), ii) nuclear retention of RNAs that are defective or immature (Zhang and Carmichael, 2001), iii) DNA non-homologous end joining (NHEJ) recombination required for double-strand break repair and V(D)J recombination (Salton et al, 2010) and iv) modulation of transcription and translation processes (Li et al, 2022). LSD1 interaction partners within infected macrophages were also enriched in ribosomal proteins, whose methylation state may be affected by LSD1 (Hamidi et al, 2018).…”