PPM1G and its diagnostic, prognostic and therapeutic potential in HCC (Review).

Global statistics indicate that hepatocellular carcinoma (HCC) is the sixth most common cancer and the third leading cause of cancer­related death. Protein phosphatase Mg2+/Mn2+ dependent 1G (PPM1G, also termed PP2Cγ) is one of the 17 members of the PPM family. The enzymatic activity of PPM1G is highly reliant on Mg2+ or Mn2+ and serves as a dephosphorylation regulator for numerous key proteins. PPM1G, functioning as a phosphatase, is involved in a number of significant biological processes such as the regulation of eukaryotic gene expression, DNA damage response, cell cycle and apoptosis, cell migration ability, cell survival and embryonic nervous system development. Additionally, PPM1G serves a role in regulating various signaling pathways. In recent years, further research has increasingly highlighted PPM1G as an oncogene in HCC. A high expression level of PPM1G is closely associated with the occurrence, progression and poor prognosis of HCC, offering notable diagnostic and therapeutic value for this patient population. In the present review, the regulatory role of PPM1G in diverse biological processes and signaling pathway activation in eukaryotes is evaluated. Furthermore, its potential application as a biomarker in the diagnosis and prognosis evaluation of HCC is assessed, and future prospects for HCC treatment strategies centered on PPM1G are discussed.

CircWHSC1 (CircNSD2): A Novel Circular RNA in Multiple Cancers.

Circular RNAs (circRNAs) are a type of non-coding RNA (ncRNA) that possesses a unique single-stranded circular structure. They are primarily formed through alternative splicing of pre-mRNA (messenger RNA). The primary biological function of circRNAs is to regulate gene expression at both the transcriptional and post-transcriptional levels. Recent studies have increasingly demonstrated a close association between the dysregulation of circRNAs and the progression of diverse cancers, where they can function as either tumor suppressors or oncogenes. circWHSC1 (circNSD2) is a circular ncRNA that originates from the first 2 exons of the Wolf-Hirschhorn syndrome candidate gene (WHSC1). As Chen 2019 discovery that circWHSC1 (circNSD2) functions as a sponge for miRNAs and promotes cancer, this circRNA has garnered significant interest among researchers. circWHSC1 (circNSD2) has been found to be up-regulated in various malignant tumors, including nasopharyngeal carcinoma, lung cancer, breast cancer, liver cancer, colorectal cancer, ovarian cancer, cervical cancer, and endometrial cancer. It exerts its effects on cancer by either inhibiting or promoting the expression of related genes through direct or indirect pathways, ultimately affecting cancer proliferation, invasion, and prognosis. This article provides a comprehensive review and discussion of the biological roles of circWHSC1 (circNSD2) and its target genes in various cancers, as well as the latest research progress on related molecular biological regulatory mechanisms. Furthermore, the potential significance of circWHSC1 (circNSD2) in future clinical applications and transformations is thoroughly analyzed and discussed.

Research progress on the relationship between bile acid metabolism and type 2 diabetes mellitus.

Bile acids, which are steroid molecules originating from cholesterol and synthesized in the liver, play a pivotal role in regulating glucose metabolism and maintaining energy balance. Upon release into the intestine alongside bile, they activate various nuclear and membrane receptors, influencing crucial processes. These bile acids have emerged as significant contributors to managing type 2 diabetes mellitus, a complex clinical syndrome primarily driven by insulin resistance. Bile acids substantially lower blood glucose levels through multiple pathways: BA-FXR-SHP, BA-FXR-FGFR15/19, BA-TGR5-GLP-1, and BA-TGR5-cAMP. They also impact blood glucose regulation by influencing intestinal flora, endoplasmic reticulum stress, and bitter taste receptors. Collectively, these regulatory mechanisms enhance insulin sensitivity, stimulate insulin secretion, and boost energy expenditure. This review aims to comprehensively explore the interplay between bile acid metabolism and T2DM, focusing on primary regulatory pathways. By examining the latest advancements in our understanding of these interactions, we aim to illuminate potential therapeutic strategies and identify areas for future research. Additionally, this review critically assesses current research limitations to contribute to the effective management of T2DM.

Case Report: Identification of a novel NTRK3-AJUBA fusion co-existing with ETV6-NTRK3 fusion in papillary thyroid carcinoma.

NTRK fusions are validated oncogenic drivers of various adult and pediatric tumor types, including thyroid cancer, and serve as a therapeutic target. Recently, tropomyosin receptor kinase (TRK) inhibitors, such as entrectinib and larotrectinib, display promising therapeutic efficacy in NTRK-positive solid tumors. Although some NTRK fusion partners have been identified in thyroid cancer, the spectrum of NTRK fusion is not fully characterized. In this study, a dual NTRK3 fusion was identified by targeted RNA-Seq in a 47-year-old female patient with papillary thyroid carcinoma. The patient harbors a novel in-frame fusion between NTRK3 exon 13 and AJUBA exon 2, co-existing with a known in-frame fusion between ETV6 exon 4 and NTRK3 exon 14. The dual NTRK3 fusion was validated by Sanger sequencing and fluorescence in situ hybridization (FISH) but lack TRK protein expression as defined by pan-TRK immunohistochemistry (IHC). We supposed the pan-TRK IHC result to be falsely negative. In conclusion, we present the first case of a novel NTRK3-AJUBA fusion co-existing with a known ETV6-NTRK3 fusion in thyroid cancer. These findings extend the spectrum of translocation partners in NTRK3 fusion, and the effect of dual NTRK3 fusion on TRK inhibitor therapy and prognosis needs long-term follow-up.