Background: Long non-coding RNAs modulate tumor occurrence through different molecular mechanisms. It had been reported that HNF1A-AS1 (HNF1A Antisense RNA 1) was differently expressed in multiple tumors. The role of HNF1A-AS1 in colorectal cancer was less analyzed, and the mechanism of regulating the cell cycle has not been completely elucidated. Methods: Differentially expressed lncRNAs were screened out from the TCGA database. HNF1A-AS1 was examined in CRC clinical samples and cell lines by RT-qPCR. CCK8 assay, colony formation assay, flow cytometry, transwell assays, tube forming assay and vivo experiments were performed to study the function of HNF1A-AS1 in CRC tumor progression. Bioinformatic analysis, luciferase report assay, RNA pull-down and RIP assays were carried out to explore proteins binding HNF1A-AS1 and the potential downstream targets. Results: Our results showed that HNF1A-AS1 was upregulated in CRC and associated with unfavorable prognosis. HNF1A-AS1 promoted proliferation, migration and angiogenesis, accelerated cell cycle and reduced cell apoptosis in CRC. Bioinformatics prediction and further experiments proved that HNF1A-AS1 could promote CCND1 expression by suppressing PDCD4 or competitively sponging miR-93-5p. Meanwhile, METTL3 mediated HNF1A-AS1 m⁶A modification and affected its RNA stability. HNF1A-AS1/IGF2BP2/CCND1 may act as a complex to regulate the stability of CCND1. Conclusion: In summary, our result reveals the novel mechanism in which m⁶A-mediated HNF1A-AS1/IGF2BP2/CCND1 axis promotes CRC cell cycle progression, along with competitively sponging miR-93-5p to upregulate CCND1, demonstrating its significant role in cell cycle regulation and suggesting that HNF1A-AS1 may act as a potential prognostic marker of colorectal cancer in the future.

The Hippo signaling pathway was found coordinately modulates cell regeneration and organ size. Its dysregulation contributes to uncontrolled cell proliferation and malignant transformation. YAP/TAZ are two critical effectors of the Hippo pathway and have been demonstrated essential for the initiation or growth of most tumors. Noncoding RNAs (ncRNAs), including miRNAs, lncRNAs, and circRNAs, have been shown to play critical roles in the development of many cancers. In the past few decades, a growing number of studies have revealed that ncRNAs can directly or indirectly regulate YAP/TAZ signaling. YAP/TAZ also regulate ncRNAs expression in return. This review summarizes the interactions between YAP/TAZ signaling and noncoding RNAs together with their biological functions on cancer progression. We also try to describe the complex feedback loop existing between these components.

Long non-coding RNAs (lncRNAs) are important regulators and biomarkers of tumorigenesis and tumor metastasis. Long intergenic non-protein-coding RNA 467 (LINC00467) is associated with various cancers. However, the role and mechanism of LINC00467 in colorectal cancer (CRC) promotion are poorly understood. This study aimed to present new details of LINC00467 in the progression of CRC. Reverse transcription–polymerase chain reaction demonstrated that the expression level of LINC00467 in CRC tissues and cell lines was significantly upregulated, which was closely related to the clinical features of CRC. Cell and animal studies showed that the downregulation of LINC00467 expression in CRC cells significantly inhibited cell proliferation, metastasis, and angiogenesis. Moreover, the overexpression of LINC00467 accelerated CRC promotion. Bioinformatics analysis and luciferase reporter assay confirmed that LINC00467 binds to miR-128-3p. Rescue experiments manifested that decreased miR-128-3p level reversed CRC cell inhibition by silencing LINC00467. Furthermore, vascular endothelial growth factor C (VEGFC) was identified as a target of miR-128-3p that could reverse the inhibition of cell growth that is mediated by miR-128-3p. Altogether, our results showed that LINC00467 contributes to CRC progression and angiogenesis via the miR-128-3p/VEGFC axis. Our findings expand the understanding of the mechanisms underlying CRC and suggest potential targets for clinical strategies against CRC. Graphical abstract

Rationale: Treatment of recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC) remains challenging, especially after resistance develops to conventional chemotherapy, radiotherapy, and targeted agents. Novel formulations, such as polymeric micellar paclitaxel (pm-Pac), which offer a Cremophor-free delivery system, warrant investigation in salvage settings to overcome resistance and improve outcomes. Patient concerns: Two patients with locally advanced HNSCC experienced multiple disease recurrences following several surgical resections. Both had received prior taxane-based chemotherapy alongside radiotherapy, anti-EGFR therapy, and immunotherapy, yet developed progressive disease, highlighting the clinical dilemma of managing multiply relapsed, treatment-refractory HNSCC. Diagnoses: Both patients were diagnosed with R/M HNSCC, demonstrated low PD-L1 expression (TPS 2% and 3%, respectively), and negative EBER status. Interventions: Following progression on multiple prior lines of therapy, both patients received salvage regimens containing pm-Pac in combination with platinum, fluorouracil, and either an immune checkpoint inhibitor (tislelizumab, case 1) or a tyrosine kinase inhibitor (lenvatinib, case 2). The treatment was administered for 6 cycles, followed by maintenance therapy. Outcomes: The pm-Pac-based combination therapy achieved significant tumor regression. In case 1 (ear canal primary), the target lesion was reduced by 43.1%, resulting in a progression-free survival (PFS) of 8.2 months. In case 2 (laryngeal primary), a 59.1% reduction was observed, with a PFS of approximately 11 months. Treatment was generally tolerable, with manageable grade 2 neutropenia as the primary adverse event. Lessons: These 2 cases suggest that reintroducing paclitaxel in its novel polymeric micellar formulation, pm-Pac, within a combination regimen may overcome prior resistance and provide meaningful disease control in heavily pretreated R/M HNSCC patients. This approach represents a potentially viable salvage strategy, warranting further clinical investigation to confirm its efficacy and optimal integration into the treatment sequence for refractory HNSCC.