MiRNA-296-5p promotes the sensitivity of nasopharyngeal carcinoma cells to cisplatin via targeted inhibition of STAT3/KLF4 signaling axis.

Improving drug sensitivity is an important strategy in chemotherapy of cancer and accumulating evidence indicates that miRNAs are involved in the regulation of drug sensitivity, but the specific mechanism is still unclear. Our previous study has found that miR-296-5p was significantly downregulated in nasopharyngeal carcinoma (NPC). Here, we aim to explore whether miR-296-5p is involved in regulating cisplatin sensitivity in NPC by regulating STAT3/KLF4 signaling axis. The cell proliferation and clonogenic capacity of NPC cells were evaluated by CCK8 Assay and plate colony assay, respectively. The Annexin V-FITC staining kit was used to determine and quantify the apoptotic cells using flow cytometry. The drug efflux ability of NPC cells were determined by Rhodamine 123 efflux experiment. The expression of miR-296-5p, apoptosis-related genes and protein in NPC cell lines were detected by qPCR and Western blot, respectively. Animal study was used to evaluate the sensitivity of NPC cells to DDP treatment in vivo. Our results showed that elevated miR-296-5p expression obviously promoted the sensitivity of NPC cells to DDP by inhibiting cell proliferation and clonogenic capacity, and inducing apoptosis. In addition, we found that miR-296-5p inhibited the expression of STAT3 and KLF4 in NPC cells, while overexpression of exogenous STAT3 reversed miR-296-5p-mediated enhancement in cell death of DDP-treated NPC cells. In vivo studies further confirmed that miR-296-5p promotes the sensitivity of NPC cells to DDP treatment. miRNA-296-5p enhances the drug sensitivity of nasopharyngeal carcinoma cells to cisplatin via STAT3/KLF4 signaling pathway.

MicroRNA-199a-3p suppresses the invasion and metastasis of nasopharyngeal carcinoma through SCD1/PTEN/AKT signaling pathway.

MicroRNAs (miRs) are 18-25 nucleotides non-coding RNAs, which contribute to tumorigenesis. Previous studies have demonstrated that miR-199a-3p is dysregulated in human nasopharyngeal carcinoma (NPC), but its role in NPC progression still largely unknown. The current study aimed to determine the potential role of miR-199a-3p in NPC progression and the underlying mechanisms. In this study, miR-199a-3p was found to be prominently down-regulated in NPC tissues and cells. The cellular assay showed that transfection of miR-199a-3p markedly repressed the migration, invasion and induced epithelial-mesenchymal transition (EMT) in both 5-8F and CNE-2 cell lines. By dual-luciferase reporter, western blotting and gas chromatography assays, we found that SCD1 is not only highly expressed in NPC tissues and negatively associated with the prognosis of NPC patients but also can be apparently downregulated by miR-199a-3p in NPC cells, suggesting that SCD1 is a direct target gene of miR-199a-3p. Moreover, inhibition of miR-199a-3p expression activated PI3K/Akt signaling and up-regulated the expression of MMP-2. With tumor xenograft models in nude mice, we also showed that miR-199a-3p repressed tumor growth in vivo. Our study demonstrated that miR-199a-3p inhibited migration and invasion of NPC cells through downregulating SCD1 expression, thus providing a potential target for the treatment of NPC.

Durable response of tislelizumab plus cisplatin, nab-paclitaxel followed by concurrent chemoradiotherapy in locoregionally advanced nasopharyngeal carcinoma: A case report.

RATIONALE: Limited patients with locoregionally advanced nasopharyngeal carcinoma (LA-NPC) have achieved complete response (CR) from induction chemotherapy (IC). Neoadjuvant immunotherapy combined with chemotherapy has marked therapeutic effects in some locoregionally advanced solid tumors. However, its efficacy and safety of NPC have not been reported so far. The rapid response of neoadjuvant tislelizumab combined with chemotherapy on LA-NPC may be associated with long-term survival benefit. PATIENT CONCERNS: A 57-year-old male patient presented with a 2-month history of bloody nasal discharge and right neck mass for 2 weeks. DIAGNOSIS: The patient was eventually diagnosed with nasopharyngeal nonkeratinizing undifferentiated cell carcinoma (stage IVA). INTERVENTIONS: The patient received tislelizumab combined with nanoparticle albumin-bound paclitaxel (nab-paclitaxel) nab-paclitaxel plus cisplatin for 4 cycles, followed by cisplatin-based concurrent chemoradiotherapy (CCRT). OUTCOMES: A partial response (PR) was achieved after 2 cycles of tislelizumab and nab-paclitaxel plus cisplatin, and CR was achieved after 4 cycles of neoadjuvant treatment. The duration of response lasted 24 months, and the patient was still in CR as of November 2022. The patient had no serious adverse event (AEs) during the treatment. LESSONS: This case report showed that tislelizumab combined with cisplatin plus nab-paclitaxel followed CCRT for treatment of patients with LA-NPC may receive a fast and durable response with a manageable safety profile and long-term survival.

Author Correction: Diversity in gut bacterial community of school-age children in Asia.

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Diversity in gut bacterial community of school-age children in Asia.

Asia differs substantially among and within its regions populated by diverse ethnic groups, which maintain their own respective cultures and dietary habits. To address the diversity in their gut microbiota, we characterized the bacterial community in fecal samples obtained from 303 school-age children living in urban or rural regions in five countries spanning temperate and tropical areas of Asia. The microbiota profiled for the 303 subjects were classified into two enterotype-like clusters, each driven by Prevotella (P-type) or Bifidobacterium/Bacteroides (BB-type), respectively. Majority in China, Japan and Taiwan harbored BB-type, whereas those from Indonesia and Khon Kaen in Thailand mainly harbored P-type. The P-type microbiota was characterized by a more conserved bacterial community sharing a greater number of type-specific phylotypes. Predictive metagenomics suggests higher and lower activity of carbohydrate digestion and bile acid biosynthesis, respectively, in P-type subjects, reflecting their high intake of diets rich in resistant starch. Random-forest analysis classified their fecal species community as mirroring location of resident country, suggesting eco-geographical factors shaping gut microbiota. In particular, children living in Japan harbored a less diversified microbiota with high abundance of Bifidobacterium and less number of potentially pathogenic bacteria, which may reflect their living environment and unique diet.