Biology subjects

Azharuddin, M.

Publications and source records attributed to Azharuddin, M..

5 recordsLinked to original sources

bioRxiv2026

Dual-compartment engagement of STAR-family proteins SAM68 and QKI by LINC00941 sustains oncogenic fitness in RAS-driven lung cancer

Long non-coding RNAs (lncRNAs) are increasingly recognised as effectors of oncogenic signalling, yet the transcriptional programmes through which driver mutations regulate lncRNA expression remain poorly defined. Here we identify LINC00941 as a direct transcriptional target of FOSL1, an AP-1 transcription factor downstream of the KRAS-MAPK pathway, establishing the first FOSL1-regulated lncRNA in lung adenocarcinoma (LUAD). LINC00941 is significantly upregulated in LUAD across multiple independent cohorts, and its depletion via siRNAs, shRNAs, and antisense oligonucleotides (ASOs) induces proliferative arrest and stress-induced premature senescence, accompanied by transcriptomic suppression of cell cycle and DNA damage response (DDR) genes. Mechanistically, LINC00941 operates through a dual-compartment mechanism engaging two STAR-family RNA-binding proteins in distinct subcellular contexts. In the nucleus, LINC00941 binds SAM68 through its 700-1300 nucleotide region and shields it from proteasomemediated degradation, thereby sustaining SAM68-dependent PARP1 activation and DDR competency; RNF123 is identified as a candidate E3 ligase mediating SAM68 turnover in the absence of LINC00941. In the cytoplasm, LINC00941 sequesters QKI, preventing its nuclear translocation; LINC00941 depletion releases QKI to the nucleus, driving alternative splicing dysregulation including validated NUMB exon 12 exclusion, and QKI co-depletion rescues the anti-proliferative phenotype both in vitro and in xenograft models. Multi-cohort survival analysis across three independent LUAD datasets (n=649) identifies LINC00941 as an independent prognostic factor for poor overall survival. Gymnotic ASO-mediated targeting of LINC00941 significantly suppresses xenograft tumour growth without systemic toxicity, providing preclinical proof-of-concept for therapeutic tractability. Together, these findings establish LINC00941 as a compartment-specific oncogenic scaffold within the KRAS-FOSL1 transcriptional axis and a tractable therapeutic target in LUAD.

cancer biology↗

bioRxiv2021

Long-lasting humoral immunity in Covid-19 infected patients at a University Hospital Clinic in Ostergotland County Council during 2020-2021.

Longitudinal serum samples and nasopharyngeal/nasal swab samples were collected from forty-eight individuals (median age 66yrs) with Covid-19 PCR-positive test results at Linkoping University Hospital. Samples were collected from initial visit and for 6 months follow up. Presence of serum IgG and IgA against SARS-CoV-2 antigens (S1-spike, nucleocapsid and NSP3) were analyzed. Nasal swabs were tested for presence of IgA against the outer envelope S1 spike protein. Ninety-two percent of participants were seropositive against SARS-CoV-2 recombinant proteins at day 28 from study entry and all (100%) were seropositive from samples collected at 2 months or later. The most common antibody responses (both serum IgG, mainly IgG1 and IgA) were detected against the S1-spike protein and the nucleoprotein. In samples collected from nasal tissues considerably lower frequencies of IgA-positive reactivities were detected. Sixteen to 18 percent of study participants showed detectable IgA levels in nasal samples, except at day 60 when 36% of tested individuals showed presence of IgA against the S1-spike protein. The study suggests that the absolute majority of studied naturally infected Covid-19 patient in the Linkoping, Ostergotland health region develop over 6 months lasting detectable levels of serum IgG and IgA responses towards the SARS-CoV-2 S1-spike protein as well as against the nucleoprotein, but not against the non-structural protein 3.

immunology↗

bioRxiv2019

Collagen-based scaffolds with infused anti-VEGF release system as potential cornea substitute for high-risk keratoplasty: An in vitro evaluation

Currently the only widely accepted corneal blindness treatment is to replace it by transplantation with human donor cornea. However, increasing shortage of donor corneas as well as high risk of rejection in some corneal diseases remain two major problems, which limit the success of corneal transplantation. Corneal neovascularization is considered as one of the main risk factors of graft failure. Different cell-free biosynthetic scaffolds fabricated from collagens or collagen-like peptides are being tested as donor cornea substitutes (DCS). Here, we report for the first-time composite biosynthetic DCS with integrated sustained release system of anti-VEGF drug, bevacizumab and their in vitro validation. We have tethered gold nanoparticles with bevacizumab and integrated into a collagen-based cell-free hydrogel scaffold. Developed grafts preserved good optical properties and were confirmed not toxic to human corneal epithelial cells. Bevacizumab has been shown to constantly releasing from the DCS up to 3 weeks and preserved its anti-angiogenic properties. These results provide background for further use of infused composite biosynthetic DCS with integrated nanosystem of bevacizumab sustained release in corneal disease accompanied by neovascularisation where conventional corneal transplantation might fail.

bioengineering↗

bioRxiv2019

Multicellular tumor spheroids- an effective in vitro model for understanding drug resistance in head and neck cancer

A hallmark of cancer is the ability to develop resistance against therapeutic agents. Therefore, developing effective in vitro strategies to identify drug resistance remains of paramount importance for treatment success. A way cancer cells achieve drug resistance is through the expression of efflux pumps that actively pump drugs out of the cells. To date, several studies have investigated the potential of using 3D multicellular tumor spheroids (MCSs) to assess drug resistance; however, a unified system that uses MCSs to differentiate between multi drug resistant (MDR) and non-MDR cells does not exist. In the present report, we have used MCSs obtained from post-diagnosed, pre-treated (PDPT) patient derived head and neck squamous cancer cells that often become treatment resistant, to develop an integrated approach combining clinical drug response and cytotoxicity screening, real-time drug uptake monitoring, and drug transporter activity assessment using flow cytometry in the presence and absence of their respective specific inhibitors. The present report shows a comparative response to MDR, drug efflux capability, and reactive oxygen species (ROS) activity to assess the resistance profile of PDPT patient-derived MCSs and two-dimensional cultures of the same set of cells. We show that MCSs serve as robust and reliable models for the clinical evaluation of drug resistance. Our proposed strategy can thus have potential clinical applicability for profiling drug resistance in cancers with unknown resistance profiles, which consequentially can indicate benefit from downstream therapy.

cancer biology↗

bioRxiv2019

Rational nanotoolbox with theranostic potential for medicated pro-regenerative corneal implants

Cornea diseases are a leading cause of blindness and the disease burden is exacerbated by the increasing shortage around the world for cadaveric donor corneas. Despite the advances in the field of regenerative medicine, successful transplantation of laboratory made artificial corneas has not been fully realised in clinical practice. The causes of failure of such artificial corneal implants are multifactorial and include latent infections from viruses and other micorbes, enzyme over-expression, implant degradation, extrusion or delayed epithelial regeneration. Therefore, there is an urgent unmet need for developing customized corneal implants to suit the host environment, counter the effects of inflammation or infection and that are able to track early signs of implant failure in situ. In the present work, we describe a nano toolbox comprising tools for drug release and in addition capable of being infection responsive, promoting regeneration including non-invasive monitoring of in situ corneal environment. These nano constructs can be incorporated within pro-regenerative biosynthetic implants, transforming them into theranostic devices able to respond to biological changes following implantation.

biochemistry↗